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  • 1. Abbas, Sascha
    et al.
    Linseisen, Jakob
    Rohrmann, Sabine
    Chang-Claude, Jenny
    Peeters, Petra H
    Engel, Pierre
    Brustad, Magritt
    Lund, Eiliv
    Skeie, Guri
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Kaaks, Rudolf
    Boeing, Heiner
    Buijsse, Brian
    Adarakis, George
    Ouranos, Vassilis
    Trichopoulou, Antonia
    Masala, Giovanna
    Krogh, Vittorio
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Buckland, Genevieve
    Suárez, Marcial Vicente Argüelles
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Amiano, Pilar
    Manjer, Jonas
    Wirfält, Elisabet
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Bueno-de-Mesquita, H B
    van Duijnhoven, Fränzel J B
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Fedirko, Veronika
    Romieu, Isabelle
    Gallo, Valentina
    Norat, Teresa
    Wark, Petra A
    Riboli, Elio
    Dietary intake of vitamin D and calcium and breast cancer risk in the European prospective investigation into cancer and nutrition2013Ingår i: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 65, nr 2, s. 178-187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. During a mean follow-up of 8.8 yr, 7760 incident invasive breast cancer cases were identified among 319,985 women. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for pre- and postmenopausal breast cancer risk. Comparing the highest with the lowest quintile of vitamin D intake, HR and 95% CI were 1.07 (0.87-1.32) and 1.02 (0.90-1.16) for pre- and postmenopausal women, respectively. The corresponding HR and 95% CIs for calcium intake were 0.98 (0.80-1.19) and 0.90 (0.79-1.02), respectively. For calcium intake in postmenopausal women, the test for trend was borderline statistically significant (P(trend) = 0.05). There was no significant interaction between vitamin D and calcium intake and cancer risk (P(interaction) = 0.57 and 0.22 in pre- and postmenopausal women, respectively). In this large prospective cohort, we found no evidence for an association between dietary vitamin D or calcium intake and breast cancer risk.

  • 2. Ademuyiwa, Adesoji O.
    et al.
    Arnaud, Alexis P.
    Drake, Thomas M.
    Fitzgerald, J. Edward F.
    Poenaru, Dan
    Bhangu, Aneel
    Harrison, Ewen M.
    Fergusson, Stuart
    Glasbey, James C.
    Khatri, Chetan
    Mohan, Midhun
    Nepogodiev, Dmitri
    Soreide, Kjetil
    Gobin, Neel
    Freitas, Ana Vega
    Hall, Nigel
    Kim, Sung-Hee
    Negeida, Ahmed
    Khairy, Hosni
    Jaffry, Zahra
    Chapman, Stephen J.
    Tabiri, Stephen
    Recinos, Gustavo
    Amandito, Radhian
    Shawki, Marwan
    Hanrahan, Michael
    Pata, Francesco
    Zilinskas, Justas
    Roslani, April Camilla
    Goh, Cheng Chun
    Irwin, Gareth
    Shu, Sebastian
    Luque, Laura
    Shiwani, Hunain
    Altamimi, Afnan
    Alsaggaf, Mohammed Ubaid
    Spence, Richard
    Rayne, Sarah
    Jeyakumar, Jenifa
    Cengiz, Yucel
    Raptis, Dmitri A.
    Fermani, Claudio
    Balmaceda, Ruben
    Marta Modolo, Maria
    Macdermid, Ewan
    Chenn, Roxanne
    Yong, Cheryl Ou
    Edye, Michael
    Jarmin, Martin
    D'amours, Scott K.
    Iyer, Dushyant
    Youssef, Daniel
    Phillips, Nicholas
    Brown, Jason
    Dickfos, Marilla
    Mitul, Ashrarur Rahman
    Mahmud, Khalid
    Oosterkamp, Antje
    Assouto, Pamphile A.
    Lawani, Ismail
    Souaibou, Yacoubou Imorou
    Devadasar, Giridhar H.
    Chong, Chean Leung
    Qadir, Muhammad Rashid Minhas
    Aung, Kyaw Phyo
    Yeo, Lee Shi
    Castillo, Vanessa Dina Palomino
    Munhoz, Monique Moron
    Moreira, Gisele
    Palomino Castillo, Vanessa Dina
    Barros De Castro Segundo, Luiz Carlos
    Khouri Ferreira, Salim Anderson
    Careta, Maira Cassa
    Araujo, Rafael
    Menegussi, Juliana
    Leal, Marisa
    Barroso de Lima, Caio Vinicius
    Tatagiba, Luiza Sarmento
    Leal, Antonio
    Nigo, Samuel
    Kabba, Juana
    Ngwa, Tagang Ebogo
    Brown, James
    King, Sebastian
    Zani, Augusto
    Azzie, Georges
    Firdouse, Mohammed
    Kushwaha, Sameer
    Agarwal, Arnav
    Bailey, Karen
    Cameron, Brian
    Livingston, Michael
    Horobjowsky, Alexandre
    Deckelbaum, Dan L.
    Razek, Tarek
    Montes, Irene
    Sierra, Sebastian
    Mendez, Manuela
    Isabel Villegas, Maria
    Mendoza Arango, Maria Clara
    Mendoza, Ivan
    Aristiza Ibal, Fred Alexander Naranjo
    Montoya Botero, Jaime Andres
    Quintero Riaza, Victor Manuel
    Restrepo, Jakeline
    Morales, Carlos
    Cruz, Herman
    Munera, Alejandro
    Karlo, Robert
    Domini, Edgar
    Mihanovic, Jakov
    Radic, Mihael
    Zamarin, Kresimir
    Pezelj, Nikica
    Khyrallh, Ahmed
    Hassan, Ahamed
    Shimy, Gamal
    Fahmy, Mohamed A. Baky
    Nabawi, Ayman
    Gohar, Muhammad Saad Ali Muhammad
    Elfil, Mohamed
    Ghoneem, Mohamed
    Gohar, Muhammad El-Saied Ahmad Muhammad
    Asal, Mohamed
    Abdelkader, Mostafa
    Gomah, Mahmoud
    Rashwan, Hayssam
    Karkeet, Mohamed
    Gomaa, Ahmed
    Hasan, Amr
    Elgebaly, Ahmed
    Saleh, Omar
    Fattah, Ahmad Abdel
    Gouda, Abdullah
    Elshafay, Abd Elrahman
    Gharib, Abdalla
    Hanafy, Mohammed
    Al-Mallah, Abdullah
    Abdulgawad, Mahmoud
    Baheeg, Mohamad
    Alhendy, Mohammed
    Fattah, Ibrahim Abdel
    Kenibar, Abdalla
    Osman, Omar
    Gemeah, Mostafa
    Mohammed, Ahmed
    Adel, Abdalrahman
    Mesreb, Ahmed Maher Menshawy
    Mohammed, Abdelrahman
    Sayed, Abdelrahman
    Abozaid, Mohamed
    Kotb, Ahmed Hafez El-Badri
    Ata, Ali Amin Ahmed
    Nasr, Mohammed
    Alkammash, Abdelrahman
    Saeed, Mohammed
    El Hamid, Nader Abd
    Attia, Attia Mohamed
    Abd El Galeel, Ahmed
    Elbanby, Eslam
    El-Dien, Khalid Salah
    Hantour, Usama
    Alahmady, Omar
    Mansour, Billal
    Elkorashy, Amr Muhammad
    Taha, Emad Mohamed Saeed
    Lasheen, Kholod Tarek
    Elkolaly, Salma Said
    Abdel-Wahab, Nehal Yosri Elsayed
    Abozyed, Mahmoud Ahmed Fathi
    Adel, Ahmed
    Saeed, Ahmed Moustafa
    El Sayed, Gehad Samir
    Youssif, Jehad Hassan
    Ahmed, Soliman Magdy
    El-Shahat, Nermeen Soubhy
    Khedr, Abd El-Rahman Hegazy
    Elsebaaye, Abdelrhman Osama
    Elzayat, Mohamed
    Abdelraheim, Mohamed
    Elzayat, Ibrahim
    Warda, Mahmoud
    El Deen, Khaled Naser
    Essam, Abdelrhman
    Salah, Omar
    Abbas, Mohamed
    Rashad, Mona
    Elzayyat, Ibrahim
    Hemeda, Dalia
    Tawfik, Gehad
    Salama, Mai
    Khaled, Hazem
    Seisa, Mohamed
    Elshaer, Kareem
    Hussein, Abdelfatah
    Elkhadrawi, Mahmoud
    Afifi, Ahmed Mohamed
    Ebrahim, Osama Saadeldeen
    Metwally, Mahmoud Mohamed
    Elmelegy, Rowida
    Elsawahly, Diaa Moustafa Elbendary
    Safa, Hisham
    Nofal, Eman
    Elbermawy, Mohamed
    Raya, Metwally Abo
    Ghazy, Ahmed Abdelmotaleb
    Samih, Hisham
    Abdelgelil, Asmaa
    Abdelghany, Sarah
    El Kholy, Ahmed
    Elkady, Fatma
    Salma, Mahmoud
    Samy, Sarah
    Fakher, Reem
    Aboarab, Aya
    Samir, Ahmed
    Sakr, Ahmed
    Haroun, Abdelrahman
    Al-Aarag, Asmaa Abdel-Rahman
    Elkholy, Ahmed
    Elshanwany, Sally
    Ghanem, Esraa
    Tammam, Ahmed
    Hammad, Ali Mohamed
    El Shoura, Yousra
    El Ashal, Gehad
    Antar, Sarah
    Mehrez, Sara
    Abdelshafy, Mahmoud
    Hamad, Maha Gamal Mohamad
    Hosh, Mona
    Abdallah, Emad
    Magdy, Basma
    Alzayat, Thuraya
    Gamaly, Elsayed
    Elfeki, Hossam
    Abouzahra, Amany
    Elsheikh, Shereen
    Elgendy, Fatimah I.
    Abd El-Salam, Fathia
    Seifelnasr, Osama
    Ammar, Mohamed
    Eysa, Athar
    Sadek, Aliaa
    Toeema, Aliaa Gamal
    Nasr, Aly
    Abuseif, Mohamed
    Zidan, Hagar
    Barakat, Sara Abd Elmageed
    Elsayed, Nadin
    Abd Elrasoul, Yasmin
    El-Kelany, Ahmed
    Ammar, Mohamed Sabry
    Mustafa, Mennat-Allah
    Makhlouf, Yasmin
    Etman, Mohamed
    Saad, Samar
    Alrahawy, Mahmoud
    Raslan, Ahmed
    Morsi, Mahmoud
    Sabry, Ahmed
    Elwakil, Hager
    Shaker, Heba
    Elkelany, Ahmed
    El-Kashef, Hussein
    Shaalan, Mohamed
    Tarek, Areej
    Elwan, Ayman
    Nayel, Ahmed Ragab
    Seif, Mostafa
    Shafik, Doaa Emadeldin
    Ghoname, Mohamed Ali
    Almallah, Ahmad
    Fouad, Ahmed
    Sayma, Eman Adel
    Elbatahgy, Ahmad
    El-Ma'doul, Angham Solaiman
    Mosad, Ahmed
    Tolba, Hager
    Elsorogy, Diaa Eldin Abdelazeem Amin
    Mostafa, Hassan Ali
    Omar, Amira Atef
    Abd El Hameed, Ola Sherief
    Lasheen, Ahmed
    Abd El Salam, Yasser
    Morsi, Ashraf
    Ismail, Mohammed
    Ahmed, Hager
    Amer, Mohamed A.
    El-Hamouly, Ahmed Sabry
    Attallah, Noura
    Mosalum, Omnia
    Afandy, Ahmed
    Mokhtar, Ahmed
    Abouelnasr, Alaa
    Ayad, Sara
    Shaker, Ramdan
    Sakr, Rokia
    Amreia, Mahmoud
    Elsobky, Soaad
    Mustafa, Mohamed
    El Magd, Ahmed Abo
    Marey, Abeer
    Tarek, Amr
    Fadel, Mohamed
    Mohamed, Mohamed Moamen
    Fadel, Amr
    Ahmed, Emad Ali
    Ali, Ahmad
    Alwafai, Mohammad Ghassan
    Alnawam, Ehab Abdulkader Hemida Ghazy
    Dwydar, Abdullah
    Kharsa, Sara
    Mamdouh, Ehab
    El-Sheemy, Hatem
    Alyoussef, Ibrahim
    Aly, Abouelatta Khairy
    Aldalaq, Ahmad
    Alnawam, Ehab
    Alkhabbaz, Dalia
    Saad, Mahmoud
    Hussein, Shady
    Elazayem, Ahmed Abo
    Meshref, Ahmed
    Elashmawy, Marwa
    Mousa, Mohammed
    Nashaat, Ahmad
    Ghanem, Sara
    Elsayed, Zaynab M.
    Elwaey, Aya
    Elkadsh, Iman
    Darweesh, Mariam
    Mohameden, Ahmed
    Hafez, Mennaallah
    Badr, Ahmed
    Badwy, Assmaa
    Abd El Slam, Mohamed
    Elazoul, Mohamed
    Al-Nahrawi, Safwat
    Eldamaty, Lotfy
    Nada, Fathee
    Ameen, Mohamed
    Hagar, Aya
    Elsehimy, Mohamed
    Abo-ryia, Mohammad
    Dawoud, Hossam
    El Mesery, Shorouk
    El Gendy, Abeer
    Abdelkareem, Ahmed
    Marey, Ahmed Safwan
    Allam, Mostafa
    Shehata, Sherif
    Abozeid, Khaled
    Elshobary, Marwa
    Fahiem, Ahmed
    Sarsik, Sameh
    Hashish, Amel
    Zidan, Mohamed
    Hashish, Mohamed
    Aql, Shaimaa
    Elhendawy, Abdelaziz Osman Abdelaziz
    Husseini, Mohamed
    Khater, Omar
    Kasem, Esraa Abdalmageed
    Gheith, Ahmed
    Elfouly, Yasmin
    Soliman, Ahmed Ragab
    Hani, Yasmein
    Elfouly, Nesma
    Fawzy, Ahmed
    Hassan, Ahmed
    Rashid, Mohammad
    Elsherbiny, Abdallah Salah
    Sieda, Basem
    Badwi, Nermin Mohamed
    Mohammed, Mohammed Mustafa Hassan
    Mohamed, Osama
    Habeeb, Mohammad Abdulkhalek
    Worku, Mengistu
    Starr, Nichole
    Desta, Semay
    Wondimu, Sahlu
    Abebe, Nebyou Seyoum
    Thomas, Efeson
    Asele, Frehun Ayele
    Dabessa, Daniel
    Abebe, Nebiyou Seyoum
    Zerihun, Abebe Bekele
    Scalabre, Aurelien
    Frade, Fernanda
    Irtan, Sabine
    Parent, Valentine
    Martin, Amandine
    Graffeille, Vivien
    Gaignard, Elodie
    Alimi, Quentin
    Abbo, Olivier
    Mouttalib, Sofia
    Bouali, Ourdia
    Hervieux, Erik
    Aigrain, Yves
    Botto, Nathalie
    Faure, Alice
    Fievet, Lucile
    Panait, Nicoleta
    Eyssartier, Emilie
    Schmitt, Francoise
    Podevin, Guillaume
    Muller, Cecile
    Bonnard, Arnaud
    Peycelon, Matthieu
    Abantanga, Francis
    Boakye-Yiadom, Kwaku
    Bukari, Mohammed
    Owusu, Frank
    Awuku-Asabre, Joseph
    Bray, Lemuel Davies
    Lytras, Dimitrios
    Psarianos, Kyriakos
    Bamicha, Anastasia
    Anthoulakis, Christos
    Nikoloudis, Nikolaos
    Mitroudis, Nikolaos
    Estupinian, Sergio
    Forno, Walter
    Guevara, Romeo
    Aguilera, Maria
    Mendez, Napoleon
    Mendizabal, Cesar Augusto Azmitia
    Ramazzini, Pablo
    Urquizu, Mario Contreras
    Rodriguez, Daniel Estuardo Marroquin
    Velsquez, Carlos Ivan Perez
    Merida, Sara Maria Contreras
    Regalado, Francisco
    Lopez, Mario
    Siguantay, Miguel
    Prasad, S. S.
    Kirishnan, Anand
    Gyanchandani, Nidhi
    Bhat, Sriram
    Sreedharan, Anjana
    Kinnera, S. V.
    Nadkami, Shravan
    Lakshmi, Harish Neelamraju
    Malik, Puneet
    Bin Mahamood, Abid
    Khajanchi, Monty
    Satoskar, Savni
    Satoskar, Rajeev
    Reddy, Yella
    Venugopal, Caranj
    Kumar, Sunil
    Sutanto, Eldaa Prisca Refianti
    Soeselo, Daniel Ardian
    Tedjaatmadja, Chintya
    Rahmawati, Fitriana Nur
    Mayasari, Maria
    Al-Hasani, Ruqaya Kadhim Mohammed Jawad
    Al-Hameedi, Hasan Ismael Ibraheem
    Al-Azraqi, Israa Abdullah Aziz
    Sabeeh, Lubna
    Kamil, Rahma
    Rasendran, Amoudtha
    Sheehan, Jacqueline
    Kerley, Robert
    Normile, Caoimhe
    Gilbert, Richard William
    Song, Jiheon
    Mauro, Linnea
    Dablouk, Mohammed Osman
    Kielty, Paul
    Marks, Eleanor
    Gosling, Simon
    Mccarthy, Michelle
    Mirghani, Diya
    Naqvi, Syed Altaf
    Wong, Chee Siong
    Gosling, Simon George
    Fahy, Ciara
    Cadogan, Diana Duarte
    Powell, Anna
    Gilbert, Richard
    Clifford, Caroline
    Driscoll, Aoife
    Paul, Stassen
    Lee, Chris
    Bowe, Ross
    Hutch, William
    Mohan, Helen
    O'Neill, Maeve
    Mealy, Kenneth
    Danelli, Piergiorgio
    Bondurri, Andrea
    Maffioli, Anna
    Bonavina, Luigi
    Macchitella, Yuri
    Ceriani, Chiara
    Veronese, Ezio
    Bortolasi, Luca
    Hasheminia, Alireza
    Benevento, Angelo
    Tessera, Gaetano
    Turati, Luca
    Sgroi, Giovanni
    Rausa, Emanuele
    Venskutonis, Donatas
    Bradulskis, Saulius
    Urbanavicius, Linas
    Austraite, Aiste
    Riauka, Romualdas
    Dambrauskas, Zilvinas
    Coomber, Ross
    Johnson, Kenneth
    Nowers, Jennifer
    Periasammy, Dineshwary
    Salleh, Afizah
    Das, Andre
    Tze, Reuben Goh Em
    Kumar, Milaksh Nirumal
    Abdullah, Nik Azim Nik
    Chong, Hoong Yin
    Agius, Marija
    Borg, Elaine
    Bezzina, Maureen
    Bugeja, Roberta
    Vella-Baldacchino, Martinique
    Spina, Andrew
    Psaila, Josephine
    Francois-Coridon, Helene
    Tolg, Cecilia
    Colombani, Jean-Francois
    Jacobe, Mario
    Mapasse, Domingos
    Snyder, Elizabeth
    Oumer, Ramadan
    Osman, Mohammed
    Mohammad, Aminu
    Anyanwu, Lofty-John
    Sheshe, Abdulrahman
    Adesina, Alaba
    Faturoti, Olubukola
    Taiwo, Ogechukwu
    Ibrahim, Muhammad Habib
    Nasir, Abdulrasheed A.
    Suleiman, Siyaka Itopa
    Adeniyi, Adewale
    Adesanya, Opeoluwa
    Adebanjo, Ademola
    Osuoji, Roland
    Atobatele, Kazeem
    Ogunyemi, Ayokunle
    Wiiliams, Omolara
    Oludara, Mobolaji
    Oshodi, Olabode
    Razzaq, Abdul
    Lawal, Oluwagbemiga
    Alakaloko, Felix
    Elebute, Olumide
    Osinowo, Adedapo
    Bode, Christopher
    Adesuyi, Abidemi
    Tade, Adesoji
    Adekoya, Adeleke
    Nwokoro, Collins
    Ayandipo, Omobolaji O.
    Lawal, Taiwo Akeem
    Ajao, Akinlabi E.
    Ali, Samuel Sani
    Odeyemi, Babatunde
    Olori, Samson
    Popoola, Ademola
    Adeyeye, Ademola
    Adeniran, James
    Lossius, William J.
    Havemann, Ingemar
    Thorsen, Kenneth
    Narvestad, Jon Kristian
    Wold, Trude Beate
    Nymo, Linn
    Elsiddig, Mohammed
    Dar, Manzoor
    Bhopal, Kamran Faisal
    Iftikhar, Zainab
    Furqan, Muhammad Mohsin
    Nighat, Bakhtiar
    Jawaid, Masood
    Khalique, Abdul
    Zil-E-Ali, Ahsan
    Rashid, Anam
    Aguilar, Wendy Leslie Messa
    Chiong, Jose Antonio Cabala
    Cecilia, Ana
    Bautista, Manchego
    Huaman, Eduardo
    Zegarra, Sergio
    Camacho, Rony
    Vergara Celis, Jose Maria
    Romani Pozo, Diego Alonso
    Hamasaki, Jose
    Temoche, Edilberto
    Herrera-Matta, Jaime
    Garcia Torres, Carla Pierina
    Alvarez Barreda, Luis Miguel
    Barrionuevo Ojeda, Ronald Renato
    Garaycochea, Octavio
    Mollo, Melanie Castro
    Delgado, Mitchelle Solange De Fa Tima Linares
    Fujii, Francisco
    Manchego Bautista, Ana Cecilia
    Messa Aguilar, Wendy Leslie
    Cabala Chiong, Jose Antonio
    Aranzabal Durand, Susana Yrma
    Arroyo Basto, Carlos Alejandro
    Urbina Rojas, Nelson Manuel
    Shu Yip, Sebastian Bernardo
    Contreras Vergara, Ana Lucia
    Rosas Moran, Andrea Echevarria
    Borda Luque, Giuliano
    Rodriguez Castro, Manuel
    Alvarado Jaramillo, Ramon
    Sila, George Manrique
    Lopez, Crislee Elizabeth
    De Leon, Mardelangel Zapata Ponze
    Machaca, Massiell
    Coasaca Huaraya, Ronald
    Arenas, Andy
    Herrera Puma, Clara Milagros
    Pino, Wilfredo
    Hinojosa, Christian
    Ponze De Leon, Melanie Zapata
    Limache, Susan
    Manrrique Sila, George
    Mercado Rodriguez, Layza-Alejandra
    Sauvat, Frederique
    Vida, Lucian Corneliu
    Muntean, Liviu Iuliu
    Mironescu, Aurel Sandu
    Alomar, Ibrahim N.
    Alnuqaydan, Saleh A.
    Altwigry, Abdulrahman M.
    Othman, Moayad
    Osman, Nohad
    Alqahtani, Enas
    Alzahrani, Mohammed
    Alyami, Rifan
    Aljohani, Emad
    Alhabli, Ibrahim
    Mikwar, Zaher
    Almuallem, Sultan
    Nawawi, Abrar
    Bakhaidar, Mohamad
    Maghrabi, Ashraf A.
    Alsaggaf, Mohammed
    Aljiffry, Murad
    Altaf, Abdulmalik
    Khoja, Ahmad
    Habeebullah, Alaa
    Akeel, Nouf
    Ghandora, Nashat
    Almoflihi, Abdullah
    Huwait, Abdulmalik
    Al-Shammari, Abeer
    Al-Mousa, Mashael
    Alghamdi, Masood
    Adham, Walid
    Albeladi, Bandar
    Alfarsi, Muayad Ahmed
    Mahdi, Atif
    Al Awwad, Saad
    Nouh, Thamer
    Hassanain, Mazen
    Aldhafeeri, Salman
    Sadig, Nawal
    Algohary, Osama
    Aledrisy, Mohannad
    Gudal, Ahmad
    Alrifaie, Ahmad
    AlRowais, Mohammed
    Althwainy, Amani
    Shabkah, Alaa
    Alamoudi, Uthman
    Alrajraji, Mawaddah
    Alghamdi, Basim
    Aljohani, Saud
    Daqeeq, Abdullah
    Al-Faifi, Jubran J.
    Jennings, Vicky
    Ngayu, Nyawira
    Moore, Rachel
    Kong, Victor
    Sampson, Colleen
    Panieri, Eugenio
    Tun, Myint
    Mphatsoe, Albert Mohale
    Carreira, Jo-Anne
    Teasdale, Ella
    Wagener, Mark
    Botes, Stefan
    Du Plessis, Danelo
    Pagnozzi, Janet
    Quezada, Jimy Harold Jara
    Rodicio, Jose Luis
    Minguez, German
    Rodriguez-Uria, Raquel
    Ugalde, Paul
    Lopez-Arevalo, Camilo
    Barneo, Luis
    Gonzales Stuva, Jessica Patricia
    Aguilar-Jimenez, Jose
    Andres Garcia-Marin, Jose
    Ortega-Vazquez, Irene
    Rodriguez, Lorena
    Herrera, Norberto
    Arachchi, Prasad Pitigala
    Jan, Wanigasekara Senanayake Mudiyanselage Kithsiri
    Arachchige, Lalith Asanka Jayasooriya Jayasooriya
    Sivaganesh, Sivasuriya
    Samaraweera, Dulan Irusha
    Thanusan, Vimalakanthan
    Musa, Ahmed Elgaili Khalid
    Balila, Reem Mohammed Hassan
    Mohamed, Mohamed Awad Elkarim Hamad
    Ali, Hussein
    Elabdin, Hagir Zain
    Hassan, Alaa
    Mahdi, Sefeldin
    Ahmed, Hala
    Idris, Sahar Abdoun Ishag
    Elsayed, Makki
    Elsayed, Mohammed
    Mahmoud, Mohamed
    Thorarinsdottir, Hildur
    Utter, Maria
    Sundstrom, Sami Martin
    Wredberg, Cecilia
    Kjellin, Ann
    Nyberg, Johanna
    Frisk, Bjorn
    Ahlqvist, Sandra
    Bjorklund, Ida
    Hjertberg, Maria
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Andersson, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Gunnarsson, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Royson, Hanna
    Weber, Per
    Schmid, Roger
    Schivo, Debora
    Despotidis, Vasileios
    Breitenstein, Stefan
    Staerkle, Ralph F.
    Schadde, Erik
    Deichsel, Fabian
    Gerosa, Alexandra
    Nocito, Antonio
    Raptis, Dimitri Aristotle
    Mijuskovic, Barbara
    Zuber, Markus
    Eisner, Lukas
    Kruspi, Swantje
    Reinisch, Katharina Beate
    Schoewe, Christin
    Novak, Allan
    Palma, Adrian F.
    Teufelberger, Gerfried
    Balkan, Ali Zeynel Abidin
    Gumar, Mehmet
    Yavuz, Mehmet Ali
    Karabacak, Ufuk
    Lap, Gokhan
    Ozkan, Bahar Busra
    Adams, Ryan
    Morton, Robert
    Henderson, Liam
    Gratton, Ruth
    Clement, Keiran David
    Chang, Kate Yu-Ching
    McNish, David
    McIntosh, Ryan
    Milligan, William
    Skelly, Brendan
    Anderson-Knight, Hannah
    Lawther, Roger
    Onimowo, Jemina
    Shatkar, Veereanna
    Tharmalingam, Shivanee
    Woin, Evelina
    Fautz, Tessa
    Ziff, Oliver
    Dindyal, Shiva
    Arman, Sam
    Talukder, Shagorika
    Gadhvi, Vijay
    Chew, Luen Shaun
    Heath, Jonathan
    Mannu, Gurdeep Singh
    Zachariades, Dimitris-Christos
    Snaith, Ailsa Claire
    Hettiarachchi, Thusitha Sampath
    Nesaratnam, Arjun
    Wheeler, James
    Sykes, Mark
    Behar, Nebil
    Jordan, Harriet
    Arulampalam, Tan
    Shah, Apar
    Brown, Damien
    Blower, Emma
    Sutton, Paul
    Gasteratos, Konstantinos
    Vimalachandran, Dale
    Magee, Cathy
    Mcguigan, Andrew
    Mcaleer, Stephen
    Morgan, Clare
    Braungart, Sarah
    Lafferty, Kirsten
    Labib, Peter
    Tanase, Andrei
    Mangan, Clodagh
    Reza, Lillian
    Woodward, Helen
    Gouldthorpe, Craig
    Turner, Megan
    Wild, Jonathan R. L.
    Malik, Tom Am
    Proctor, Victoria K.
    Hewage, Kalon
    Davies, James
    Dubois, Andre
    Sarwary, Sayed
    Zardab, Ali
    Grant, Alan
    Mcintyre, Robert
    Tewari, Shirish
    Humm, Gemma
    Farinella, Eriberto
    Parthiban, Sunil
    Hall, Nigel J.
    Wright, Naomi J.
    Major, Christina P.
    Xerri, Thelma
    De Bono, Phoebe
    Amin, Jasim
    Farhad, Mustafa
    Camilleri-Brennan, John F.
    Robertson, Andrew G. N.
    Swann, Joanna
    Richards, James
    Jabbar, Aijaz
    Attard, Myranda
    Burns, Hannah
    Macdonald, Euan
    Baldacchino, Matthew
    Skehan, Jennifer
    Camilleri-Brennan, Julian
    Hall, Tom Falconer
    Gimzewska, Madelaine
    Mclachlan, Greta
    Shah, Jamie
    Giles, James
    Hassan, Maleeha
    Beasley, William
    Vlachogiorgos, Apostolos
    Dias, Stephen
    Maharaj, Geta
    McDonald, Rosie
    Cross, Kate
    Rees, Clare M.
    Van Duren, Bernard
    Upchurch, Emma
    Karandikar, Sharad
    Bowley, Doug
    Karim, Ahmed
    Chachulski, Witold
    Richardson, Liam
    Dawnay, Giles
    Thompson, Ben
    Mistry, Ajayesh
    Ghetia, Millika
    Roy, Sudipta
    Al-Obaedi, Ossama
    Das, Kaustuv
    Prabhudesai, Ash
    Cocker, D. M.
    Tan, Jessica Juliana
    Vivekanantham, Sayinthen
    Gillespie, Michael
    Gudlaugsdottir, Katrin
    Pezas, Theodore
    Currow, Chelise
    Kim, Matthew Young-Han
    Salama, Yahya
    Shah, Rohi
    Ibrahem, Ahmad Aboelkassem
    Ebdewi, Hamdi
    Gravante, Gianpiero
    El-Rabaa, Saleem
    Chan, Zoe
    Hassan, Zaffar
    Makinde, Misty
    Hemingway, David
    Dean, Ramzana
    Boddy, Alexander
    Aber, Ahmed
    Patel, Vijay
    Kotecha, Deevia
    Ubhi, Harmony Kaur
    Hosein, Simon-Peter
    Ward, Simon
    Malik, Kamran
    Jennings, Leifa
    Newton, Tom
    Alkhouri, Mirna
    Kang, Min Kyu
    Houlden, Christopher
    Barry, Jonathan
    Wilson, Michael S. J.
    Neo, Yan Ning
    Ibrahim, Ibrahim
    Chan, Emily
    Peck, Fraser S.
    Lim, Pei J.
    North, Alexander S.
    Blundell, Rebecca
    Williamson, Adam
    Fouad, Dina
    Minocha, Ashish
    Mccarthy, Kathryn
    Court, Emma
    Chambers, Alice
    Yee, Jenna
    Tham, Ji Chung
    Beaton, Ceri
    Walsh, Una
    Lockey, Joseph
    Bokhari, Salman
    Howells, Lara
    Griffiths, Megan
    Yallop, Laura
    Singh, Shailinder
    Nasher, Omar
    Jackson, Paul
    Ramzi, Saed
    Zeidan, Shady
    Doughty, Jennifer
    Sinha, Sidhartha
    Davenport, Ross
    Lewis, Jason
    Duffy, Leo
    Mcaleer, Elizabeth
    Williams, Eleanor
    Obute, Rhalumi Daniel
    Glover, Thomas E.
    Clark, David J.
    Boshnaq, Mohamed
    Akhtar, Mansoor
    Capleton, Pascale
    Doughan, Samer
    Rabie, Mohamed
    Mohamed, Ismail
    Samuel, Duncan
    Dickson, Lauren
    Kennedy, Matthew
    Dempster, Eleanor
    Brown, Emma
    Maple, Natalie
    Monaghan, Eimear
    Wolf, Bernhard
    Garland, Alicia
    Lund, Jonathan
    Boereboom, Catherine
    Murphy, Jennifer
    Tierney, Gillian
    Tou, Samson
    Zimmermann, Eleanor Franziska
    Smart, Neil James
    Warwick, Andrea Marie
    Stasinou, Theodora
    Daniels, Ian
    Findlay-Cooper, Kim
    Mitrasinovic, Stefan
    Ray, Swayamjyoti
    Varcada, Massimo
    D'souza, Rovan
    Omara, Sharif
    Boyce, Tamsin
    Whewell, Harriet
    Jones, Elin
    Ma, Jennifer
    Abington, Emily
    Ramcharn, Meera
    Williams, Gethin
    Winstanley, Joseph
    Kennedy, Ewan D.
    Yeung, Emily N. W.
    Fergusson, Stuart J.
    Jones, Catrin
    O'neill, Stephen
    Lim, Shujing Jane
    Liew, Ignatius
    Nair, Hari
    Fairfield, Cameron
    Oh, Julia
    Koh, Samantha
    Wilson, Andrew
    Fairfield, Catherine
    Th'ng, Francesca
    Robertson, Nichola
    Anandkumar, Delran
    Kirupagaran, Ashok
    Jones, Timothy F.
    Torrance, Hew D.
    Fowler, Alexander J.
    Chandrakumar, Charmilie
    Patel, Priyank
    Ashraf, Syed Faaz
    Lakhani, Sonam M.
    Mclean, Aaron Lawson
    Basson, Sonia
    Batt, Jeremy
    Bowman, Catriona
    Stoddart, Michael
    Benons, Natasha
    Barker, Tom
    Summerour, Virginia
    Harper, Edward
    Smith, Caroline
    Hampton, Matthew
    Mckechnie, Doug
    Farah, Ayaan
    Chun, Anita
    Pereira, Bernadette
    Nemeth, Kristof
    Decker, Emily
    Giuliani, Stefano
    Shalaby, Aly
    Szczap, Aleksandra
    Chidambaram, Swathikan
    Chen, Chee Yang
    Kulasabanathan, Kavian
    Chhabra, Srishti
    Kostov, Elisabeth
    Harbord, Philippe
    Barnacle, James
    Palliyil, Madan Mohan
    Zikry, Mina
    Porter, Johnathan
    Raslan, Charef
    Hafiz, Shazia
    Soltani, Niksa
    Baillie, Katie
    Mirza, Ahmad
    Saeed, Haroon
    Galloway, Simon
    Elena, Gia
    Afzal, Mohammad
    Zakir, Mohamed
    Sodde, Peter
    Hand, Charles
    Sriram, Aiesha
    Clark, Tamsyn
    Holton, Patrick
    Livesey, Amy
    Sinha, Yashashwi
    Iqbal, Fahad Mujtaba
    Bharj, Indervir Singh
    Rotundo, Adriana
    Jenvey, Cara
    Slade, Robert
    Golding, David
    Haines, Samuel
    Abdullah, Ali Adel Ne'ma
    Tilston, Thomas W.
    Loughran, Dafydd
    Donoghue, Danielle
    Giacci, Lorenzo
    Sherif, Mohamed Ashur
    Harrison, Peter
    Tang, Alethea
    Elshaer, Mohamed
    Urbonas, Tomas
    Riaz, Amjid
    Chapman, Annie
    Acharya, Parisha
    Shalhoub, Joseph
    Grossart, Cathleen
    McMorran, David
    Mlotshwa, Makhosini
    Hawkins, William
    Loizides, Sofronis
    Thomson, Peter
    Khan, Shahab
    Taylor, Fiona
    Shukla, Jalak
    Howie, Emma Elizabeth
    Macdonald, Linda
    Komolafe, Olusegun
    Mcintyre, Neil
    Cragg, James
    Parker, Jody
    Stewart, Duncan
    Lintin, Luke
    Tracy, Julia
    Farooq, Tahir
    Sion, Melanie
    Weinstein, Michael S.
    Punja, Viren
    Bugaev, Nikolay
    Goodstein, Monica
    Razmdjou, Shadi
    Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries2016Ingår i: BMJ Global Health, E-ISSN 2059-7908, Vol. 1, nr 4, artikel-id e000091Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.

    Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.

    Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.

    Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.

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  • 3. Agudo, Antonio
    et al.
    Bonet, Catalina
    Sala, Núria
    Muñoz, Xavier
    Aranda, Núria
    Fonseca-Nunes, Ana
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie Christine
    Vineis, Paolo
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Grioni, Sara
    Quirós, J Ramón
    Molina, Esther
    Navarro, Carmen
    Barricarte, Aurelio
    Chamosa, Saioa
    Allen, Naomi E
    Khaw, Kay-Tee
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Numans, Mattijs E
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Kaaks, Rudof
    Canzian, Federico
    Boeing, Heiner
    Meidtner, Karina
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten. WHO, IARC, Lyon, France.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Manjer, Jonas
    Overvad, Kim
    Tjonneland, Anne
    Lund, Eiliv
    Weiderpass, Elisabete
    Jenab, Mazda
    Fedirko, Veronika
    Offerhaus, G Johan A
    Riboli, Elio
    González, Carlos A
    Jakszyn, Paula
    Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2013Ingår i: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 34, nr 6, s. 1244-1250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

  • 4. Aleksandrova, Krasimira
    et al.
    Bamia, Christina
    Drogan, Dagmar
    Lagiou, Pagona
    Trichopoulou, Antonia
    Jenab, Mazda
    Fedirko, Veronika
    Romieu, Isabelle
    Bueno-de-Mesquita, H. Bas
    Pischon, Tobias
    Tsilidis, Kostas
    Overvad, Kim
    Tjønneland, Anne
    Bouton-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Kaaks, Rudolf
    Kuehn, Tilman
    Tsironis, Christos
    Papatesta, Eleni-Maria
    Saitakis, George
    Palli, Domenico
    Panico, Salvatore
    Grioni, Sara
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H.
    Weiderpass, Elisabete
    Lukic, Marko
    Braaten, Tonje
    Ramon Quiros, J.
    Lujan-Barroso, Leila
    Sanchez, Mara-Jose
    Chilarque, Maria-Dolores
    Ardanas, Eva
    Dorronsoro, Miren
    Nilsson, Lena Maria
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wallström, Peter
    Ohlsson, Bodil
    Bradbury, Kathryn E.
    Khaw, Kay-Tee
    Wareham, Nick
    Stepien, Magdalena
    Duarte-Salles, Talita
    Assi, Nada
    Murphy, Neil
    Gunter, Marc J.
    Riboli, Elio
    Boeing, Heiner
    Trichopoulos, Dimitrios
    The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition2015Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 102, nr 6, s. 1498-1508Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having >= 4 cups (600mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.

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  • 5. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Nöthlings, Ute
    Jenab, Mazda
    Fedirko, Veronika
    Kaaks, Rudolf
    Lukanova-McGregor, Annekatrin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Boffetta, Paolo
    Trepo, Elisabeth
    Westhpal, Sabine
    Duarte-Salles, Talita
    Stepien, Magdalena
    Overvad, Kim
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Lagiou, Pagona
    Bamia, Christina
    Benetou, Vassiliki
    Agnoli, Claudia
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, Bas
    Peeters, Petra H
    Gram, Inger Torhild
    Lund, Eiliv
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, María-José
    Gavrila, Diana
    Barricarte, Aurelio
    Dorronsoro, Miren
    Ohlsson, Bodil
    Lindkvist, Björn
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C
    Riboli, Elio
    Pischon, Tobias
    Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer2014Ingår i: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, nr 3, s. 858-871Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

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  • 6.
    Alkner, Sara
    et al.
    Department of Oncology, Faculty of Medicine, Institute of Clinical Sciences Lund, Lund University, Lund, Sweden; Skåne University Hospital Lund, Department of Hematology, Oncology and Radiation Physics, Lund, Sweden.
    Wieslander, Elinore
    Skåne University Hospital Lund, Department of Hematology, Oncology and Radiation Physics, Lund, Sweden.
    Lundstedt, Dan
    Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; Department of Oncology at, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Berg, Martin
    Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
    Kristensen, Ingrid
    Skåne University Hospital Lund, Department of Hematology, Oncology and Radiation Physics, Lund, Sweden.
    Andersson, Yvette
    Department of Surgery, Vastmanland Hospital Västerås, Västerås, Sweden; Centre for Clinical Research, Uppsala University and Region Vastmanland, Vastmanland Hospital Västerås, Sweden.
    Bergkvist, Leif
    Centre for Clinical Research, Uppsala University and Region Vastmanland, Vastmanland Hospital Västerås, Sweden.
    Frisell, Jan
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Breast Center Karolinska, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden.
    Olofsson Bagge, Roger
    Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Department of Surgery, University of Helsinki and Helsinki University Hospital, Finland.
    Christiansen, Peer
    Department of Plastic and Breast Surgery, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
    Davide Gentilini, Oreste
    Breast Surgery, IRCCS Ospedale San Raffaele, Milano, Italy; Vita-Salute San Raffaele University, Milano, Italy.
    Kontos, Michalis
    1st Department of Surgery, National and Kapodistrian University of Athens, Athens, Greece.
    Kühn, Thorsten
    Die Filderklinik, Breast Center, Filderstadt, Germany; Department of Gynecology and Obstetrics, University of Ulm, Germany.
    Reimer, Toralf
    Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany.
    Rydén, Lisa
    Department of Oncology, Faculty of Medicine, Institute of Clinical Sciences Lund, Lund University, Lund, Sweden; Skåne University Hospital, Department of Gastroenterology and Surgery, Malmö, Sweden.
    Filtenborg Tvedskov, Tove
    Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Breast Surgery, Gentofte Hospital, Gentofte, Denmark.
    Vrou Offersen, Birgitte
    Department of Oncology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark; Department of Experimental Clinical Oncology, Danish Center for Particle Therapy, Aarhus, Denmark.
    Dahl Nissen, Henrik
    Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
    de Boniface, Jana
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, Capio St. Goran's Hospital, Stockholm, Sweden.
    Quality assessment of radiotherapy in the prospective randomized SENOMAC trial2024Ingår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 197, artikel-id 110372Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial.

    Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1–2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015–2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.

    Results: CRF-data and RT plans agreed in 99.3 % (breast/chest wall) and in 96.6 % of patients (regional RT). Congruence for whether level I was an intended RT target was lower (78 %). In accordance with Danish national guidelines, level I was more often an intended target in the SLN biopsy only arm (N = 334/611, 55 %,) than in the cALND arm (N = 174/565, 31 %,). When an intended target, level I received prescribed dose to 100 % (IQR 98–100 %) of the volume. However, even when not an intended target, full dose was delivered to > 80 % of level I (IQR 75–90 %). The intentional inclusion of level I in the target volume more than doubled the dose received by ≥ 50 % of the humeral head.

    Conclusion: Congruence between CRF data and RT plans was excellent. Level I received a high dose coverage even when not intentionally included in the target. Including level I in target significantly increased dose to the humeral head.

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  • 7.
    Andersson, Magnus N.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Svensson, Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Björkgren, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wiberg, Rebecca
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Prophylactic mastectomy – Correlation between skin flap thickness and residual glandular tissue evaluated postoperatively by imaging2022Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1878-0539, Vol. 75, nr 6, s. 1813-1819Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Women with an increased hereditary risk of breast cancer can undergo risk-reducing prophylactic mastectomy. However, there is a balance between how much subcutaneous tissue should be resected to achieve maximal reduction of glandular tissue, while leaving viable skin flaps.

    Methods: Forty-five women previously operated with prophylactic mastectomy underwent magnetic resonance tomography (MRT) and ultrasound (US) to investigate the correlation between skin flap thickness and residual glandular tissue. Residual glandular tissue was documented as being present or not present, but not quantified, as the amount of residual glandular tissue in many cases was considered too small to make reliable volume quantifications with available tools. Since a mastectomy skin flap thickness of 5 mm is discussed as an oncologically safe thickness in the literature, this was used as a cut-off.

    Results: Following prophylactic mastectomy, residual glandular tissue was detected in 39.3% of all breasts and 27.9% of all the breast quadrants examined by MRT, and 44.1% of all breasts and 21.7% of all the breast quadrants examined by US. Residual glandular tissue was detected in 6.9% of the quadrants in skin flaps ≤ 5 mm and in 37.5% of the quadrants in skin flaps > 5 mm (OR 3.07; CI = 1.41–6.67; p = 0.005). Furthermore, residual glandular tissue increased significantly already when the skin flap thickness exceeded 7 mm.

    Conclusions: This study highlights that complete removal of glandular breast tissue during a mastectomy is difficult and suggests that this is an unattainable goal. We demonstrate that residual glandular tissue is significantly higher in skin flaps > 5 mm in comparison to skin flaps ≤ 5 mm, and that residual glandular tissue increases significantly already when the flap thickness exceeds 7 mm.

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  • 8. Andersson, Roland
    et al.
    Hellman, Per
    Johansson, Jan
    Lagergren, Jesper
    Martling, Anna
    Naredi, Peter
    Nilsson, Magnus
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Selektiv nivåstrukturering av svensk kirurgi behövs2018Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, artikel-id E76EArtikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
  • 9.
    Appelgren, Matilda
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Sackey, Helena
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Division of Cancer, Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Solna, Sweden.
    Wengström, Yvonne
    Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Solna, Sweden; Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Huddinge, Sweden.
    Johansson, Karin
    Department of Health Sciences, Lund University, Lund, Sweden.
    Ahlgren, Johan
    Department of Oncology, University Hospital, Örebro, Sweden; Regional Oncology Centre, Mid-Sweden Health Care Region, Uppsala, Sweden.
    Andersson, Yvette
    Department of Surgery, Västmanland County Hospital, Västerås, Sweden; Västmanland County Hospital, Center for Clinical Research, Uppsala University, Västerås, Sweden.
    Bergkvist, Leif
    Västmanland County Hospital, Center for Clinical Research, Uppsala University, Västerås, Sweden.
    Frisell, Jan
    Division of Cancer, Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Solna, Sweden.
    Lundstedt, Dan
    Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Rydén, Lisa
    Division of Surgery, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Department of Surgery and Gastroenterology, Skåne University Hospital, Malmö, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Alkner, Sara
    Division of Oncology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
    Vrou Offersen, Birgitte
    Department of Experimental Clinical Oncology Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Danish Breast Cancer Group Center and Clinic for Late Effects, Aarhus University Hospital, Aarhus, Denmark.
    Filtenborg Tvedskov, Tove
    Department of Breast Surgery, Rigshospitalet, Copenhagen, Denmark.
    Christiansen, Peer
    Danish Breast Cancer Group Center and Clinic for Late Effects, Aarhus University Hospital, Aarhus, Denmark; Department of Plastic and Breast Surgery, Aarhus University Hospital, Aarhus, Denmark.
    de Boniface, Jana
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, Capio St Göran's Hospital, Stockholm, Sweden.
    Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial2022Ingår i: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 63, s. 16-23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND).

    Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1–2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQ-C30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.

    Results: Overall, 976 questionnaires (501 in the SLN biopsy only group and 475 in the completion ALND group) were analysed, corresponding to a response rate of 82.6%. No significant group differences in overall HRQoL were identified. Participants receiving SLN biopsy only, reported significantly lower symptom scores on the EORTC subscales of pain, arm symptoms and breast symptoms. The Lymph-ICF domain scores of physical function, mental function and mobility activities were significantly in favour of the SLN biopsy only group.

    Conclusion: One year after surgery, arm morbidity is significantly worse affected by ALND than by SLN biopsy only. The results underline the importance of ongoing attempts to safely de-escalate axillary surgery.

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  • 10. Araghi, Marzieh
    et al.
    Galanti, Maria Rosaria
    Lundberg, Michael
    Lager, Anton
    Engström, Gunnar
    Alfredsson, Lars
    Knutsson, Anders
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Trolle Lagerros, Ylva
    Bellocco, Rino
    Pedersen, Nancy L.
    Östergren, Per-Olof
    Magnusson, Cecilia
    Use of moist oral snuff (snus) and pancreatic cancer: pooled analysis of nine prospective observational studies2017Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, nr 4, s. 687-693Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person-years of observation, 1,447 men developed pancreatic cancer. Compared to never-snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83–1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.

  • 11. Bakker, Marije F.
    et al.
    Peeters, Petra H. M.
    Klaasen, Veronique M.
    Bueno-de-Mesquita, H. Bas
    Jansen, Eugene H. J. M.
    Ros, Martine M.
    Travier, Noemie
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Rinaldi, Sabina
    Romieu, Isabelle
    Brennan, Paul
    Boutron-Ruault, Marie-Christine
    Perquier, Florence
    Cadeau, Claire
    Boeing, Heiner
    Aleksandrova, Krasimira
    Kaaks, Rudolf
    Kühn, Tilman
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Vineis, Paolo
    Krogh, Vittorio
    Panico, Salvatore
    Masala, Giovanna
    Tumino, Rosario
    Weiderpass, Elisabete
    Skeie, Guri
    Lund, Eiliv
    Ramon Quirós, J.
    Ardanaz, Eva
    Navarro, Carmen
    Amiano, Pilar
    Sánchez, María-José
    Buckland, Genevieve
    Ericson, Ulrika
    Sonestedt, Emily
    Johansson, Matthias
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. International Agency for Research on Cancer, Lyon, France.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Travis, Ruth C.
    Key, Timothy J.
    Khaw, Kay-Tee
    Wareham, Nick
    Riboli, Elio
    van Gils, Carla H.
    Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort2016Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 103, nr 2, s. 454-464Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.

    Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.

    Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin, retinol, alpha-tocopherol, gamma-tocopherol, and 454 vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.

    Results: In quintile 5 compared with quintile 1, alpha-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and beta-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for beta-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).

    Conclusion: Our results indicate that higher concentrations of plasma beta-carotene and alpha-carotene are associated with lower breast cancer risk of ER tumors.

  • 12. Bamia, Christina
    et al.
    Lagiou, Pagona
    Jenab, Mazda
    Trichopoulou, Antonia
    Fedirko, Veronika
    Aleksandrova, Krasimira
    Pischon, Tobias
    Overvad, Kim
    Olsen, Anja
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Kuhn, Tilman
    Boeing, Heiner
    Floegel, Anna
    Benetou, Vasiliki
    Palli, Domenico
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, H B As
    Dik, Vincent K
    Bhoo-Pathy, Nirmala
    Uiterwaal, Cuno S P M
    Weiderpass, Elisabete
    Lund, Eiliv
    Quirós, J Ramón
    Zamora-Ros, Raul
    Molina-Montes, Esther
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Dorronsoro, Miren
    Lindkvist, Björn
    Wallström, Peter
    Nilsson, Lena Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Khaw, Kay-Tee
    Wareham, Nick
    Bradbury, Kathryn E
    Travis, Ruth C
    Ferrari, Pietro
    Duarte-Salles, Talita
    Stepien, Magdalena
    Gunter, Marc
    Murphy, Neil
    Riboli, Elio
    Trichopoulos, Dimitrios
    Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study2015Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, nr 8, s. 1899-1908Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend = 0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend = 0.009), but not decaffeinated (p-trend = 0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects.

  • 13. Barrdahl, Myrto
    et al.
    Canzian, Federico
    Joshi, Amit D.
    Travis, Ruth C.
    Chang-Claude, Jenny
    Auer, Paul L.
    Gapstur, Susan M.
    Gaudet, Mia
    Diver, W. Ryan
    Henderson, Brian E.
    Haiman, Christopher A.
    Schumacher, Fredrick R.
    Le Marchand, Loic
    Berg, Christine D.
    Chanock, Stephen J.
    Hoover, Robert N.
    Rudolph, Anja
    Ziegler, Regina G.
    Giles, Graham G.
    Baglietto, Laura
    Severi, Gianluca
    Hankinson, Susan E.
    Lindstroem, Sara
    Willet, Walter
    Hunter, David J.
    Buring, Julie E.
    Lee, I-Min
    Zhang, Shumin
    Dossus, Laure
    Cox, David G.
    Khaw, Kay-Tee
    Lund, Eiliv
    Naccarati, Alessio
    Peeters, Petra H.
    Ramon Quiros, J.
    Riboli, Elio
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Trichopoulos, Dimitrios
    Prentice, Ross L.
    Kraft, Peter
    Kaaks, Rudolf
    Campa, Daniele
    Post-G WAS gene-environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women2014Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, nr 19, s. 5260-5270Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (P-interaction = 8.84 x 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.

  • 14. Barrdahl, Myrto
    et al.
    Canzian, Federico
    Lindström, Sara
    Shui, Irene
    Black, Amanda
    Hoover, Robert N
    Ziegler, Regina G
    Buring, Julie E
    Chanock, Stephen J
    Diver, W Ryan
    Gapstur, Susan M
    Gaudet, Mia M
    Giles, Graham G
    Haiman, Christopher
    Henderson, Brian E
    Hankinson, Susan
    Hunter, David J
    Joshi, Amit D
    Kraft, Peter
    Lee, I-Min
    Le Marchand, Loic
    Milne, Roger L
    Southey, Melissa C
    Willett, Walter
    Gunter, Marc
    Panico, Salvatore
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Weiderpass, Elisabete
    Sánchez, María-José
    Overvad, Kim
    Dossus, Laure
    Peeters, Petra H
    Khaw, Kay-Tee
    Trichopoulos, Dimitrios
    Kaaks, Rudolf
    Campa, Daniele
    Association of breast cancer risk loci with breast cancer survival2015Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, nr 12, s. 2837-2845Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; ptrend=2.84 x 10-4; HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p2DF=1.45 x 10-3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend=6.6 x 10-4; HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p2DF=1.25 x 10-4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.

    What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.

  • 15.
    Bayadsi, Haytham
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Barghout, George
    Department of Clinical Pathology, Sunderby Hospital, Sweden.
    Gustafsson, Moa
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Clinicum/Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    The expression of stromal biomarkers in small papillary thyroid carcinomas2022Ingår i: World Journal of Surgical Oncology, E-ISSN 1477-7819, Vol. 20, nr 1, artikel-id 340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The importance of stroma for tumor progression is recognized for many cancer types. In this study, we aim to evaluate the expression of types I (Col1) and IV (Col4) collagens, alpha-smooth muscle actin (a-SMA), and matrix metallopeptidase 9 (MMP-9) in the tumor stroma of small papillary thyroid carcinoma (PTC).

    MATERIAL AND METHODS: Twenty-five non-metastatic small PTCs (pT1N0) and nineteen metastatic small PTCs (pT1N1b) including corresponding metastatic lateral lymph nodes were selected and paraffinized tissue blocks retrieved. The samples were stained for Col1, COL4, a-SMA, and MMP-9 antibodies using immunohistochemistry. The expression of the stromal proteins was scored and analyzed based on the location, intensity, and distribution.

    RESULTS: Col1 and Col4 expression were significantly higher in normal thyroid tissue compared to PTC tissue. On the contrary, expression of a-SMA and MMP-9 was higher in PTC tissue compared to normal thyroid tissue. Both Col1 and Col4 were significantly more highly expressed in the non-metastatic tumors compared with metastatic tumors. The expression of a-SMA and MMP9 was slightly, but not significantly, higher in the metastasized tumors and their respective lymph nodes. There was a significant correlation between the metastasized tumors and their respective lymph nodes in Col1 and MMP-9 expression.

    CONCLUSIONS: Col1, Col4, a-SMA, and MMP-9 expression in PTCs differs significantly from that of normal thyroid tissue. The higher expression of Col1 and Col4 in normal thyroid tissue and in the non-metastasized tumors indicates that Col1 and 4 might have a potential protective role in tumor progression. The higher expression of a-SMA and MMP9 in PTCs indicates that these proteins might have a role in promoting PTC progression and aggressiveness.

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  • 16.
    Bayadsi, Haytham
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Bergman, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Invasiveness and Metastatic Aggressiveness in Small Differentiated Thyroid Cancers: Demography of Small Papillary Thyroid Carcinomas in the Swedish Population2020Ingår i: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 44, nr 2, s. 461-468Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The western world is seeing a rising incidence of thyroid cancer. Improved diagnostic methods do not entirely explain this increase. Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. Small PTC (<= 20 mm) and especially papillary thyroid microcarcinomas (PTMC <= 10 mm) are considered to be low-risk tumors but some cases are considerably more aggressive. Sufficient understanding of these mechanisms is a long-term goal for more efficient and safer treatment of these tumors.

    Methods: We identified 959 cases of small PTCs in the validated Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery, grouped according to lymph node metastasis. These were analyzed according to age, gender, tumor size and geographic region.

    Results: Patients with N1b disease (lateral lymph nodes metastases) had a smaller tumor size compared to patients with N1a disease (8.6 mm vs 10.1 mm respectively, p < 0.05). Patients and specifically females with N1b disease were younger than those with N0 or N1a disease. Patients with N1b disease had a lower proportion of females (60%) compared to N0 and N1a groups (81% and 78%, respectively). The incidence of operated small PTCs and of lymph node engagement differs between geographic regions in Sweden.

    Conclusions: Small PTC and especially PTMC seem to show different patterns of aggressiveness and demography regarding lateral lymph node metastases and 7% had N1b disease and tumor <1 cm, underscoring the importance of lymph node evaluation in PTMC patients. More understanding of predictive factors, mechanisms for metastatic disease and causes of regional differences, is needed.

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  • 17.
    Bayadsi, Haytham
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Nylén, Carolina
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Angelsten, Jakob
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Risk factors for recurrent disease in small papillary thyroid cancers: a Swedish register-based study2023Ingår i: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 408, nr 1, artikel-id 162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To study the correlation between clinicopathological risk factors and the risk for intervention-requiring cancer recurrence in patients with small papillary thyroid cancers (sPTCs). MATERIALS AND METHODS: Records for 397 patients with sPTC (T1 ≤ 20mm) were obtained from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) between 2010 and 2016. Follow-up time was at least 5 years. Data regarding intervention-requiring cancer recurrence were obtained from patient medical records and analysed regarding lymph node (LN) status (N0, N1a and N1b) and recurrence. RESULTS: Age was significantly lower in the N1a and N1b groups compared to N0 (45 vs. 40.5 vs. 49 years, respectively; p = 0.002). Tumour size was smaller in the N1a group compared to N1b group (9 vs. 11.8 mm; p <0.01). The mean number of metastatic LNs at initial surgery was higher in the N1b compared to N1a group (6.6 vs. 3; p = 0.001), and in the recurrent compared to the non-recurrent group (7 versus 3.9; p <0.01). The recurrence rate was higher in the N1b group than the N1a and N0 groups (25% vs. 2.4% vs. 1.4%, respectively; p = 0.001). CONCLUSIONS: Lymph node stage N1b at diagnosis, and having five or more metastatic nodes, are strong risk factors for cancer recurrence and decreased disease-free survival in sPTC. The management of patients with sPTC should include thorough lymph node mapping for optimal treatment and individual risk stratification.

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  • 18. Bhangu, A
    et al.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå University Hospital.
    Andersson, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå University Hospital.
    Gunnarsson, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå University Hospital.
    Escobar, EG
    Mortality of emergency abdominal surgery in high-, middle- and low-income countries2016Ingår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, nr 8, s. 971-988Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI).

    METHODS: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression.

    RESULTS: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1·6 per cent at 24 h (high 1·1 per cent, middle 1·9 per cent, low 3·4 per cent; P < 0·001), increasing to 5·4 per cent by 30 days (high 4·5 per cent, middle 6·0 per cent, low 8·6 per cent; P < 0·001). Of the 578 patients who died, 404 (69·9 per cent) did so between 24 h and 30 days following surgery (high 74·2 per cent, middle 68·8 per cent, low 60·5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2·78, 95 per cent c.i. 1·84 to 4·20) and low-income (OR 2·97, 1·84 to 4·81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days.

    CONCLUSION: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role.

  • 19. Bhoo-Pathy, Nirmala
    et al.
    Uiterwaal, Cuno S. P. M.
    Dik, Vincent K.
    Jeurnink, Suzanne M.
    Bech, Bodil H.
    Overvad, Kim
    Halkjær, Jytte
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Katzke, Verena A.
    Li, Kuanrong
    Boeing, Heiner
    Floegel, Anna
    Androulidaki, Anna
    Bamia, Christina
    Trichopoulou, Antonia
    Masala, Giovanna
    Panico, Salvatore
    Crosignani, Paolo
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H. M.
    Gavrilyuk, Oxana
    Skeie, Guri
    Weiderpass, Elisabete
    Duell, Eric J.
    Arguelles, Marcial
    Molina-Montes, Esther
    Navarro, Carmen
    Ardanaz, Eva
    Dorronsoro, Miren
    Lindkvist, Björn
    Wallström, Peter
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ye, Weimin
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Karolinska institutet.
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J.
    Travis, Ruth C.
    Duarte-Salles, Talita
    Freisling, Heinz
    Licaj, Idlir
    Gallo, Valentina
    Michaud, Dominique S.
    Riboli, Elio
    Bueno-de-Mesquita, H. Bas
    Intake of Coffee, Decaffeinated Coffee, or Tea Does Not Affect Risk for Pancreatic Cancer: Results From the European Prospective Investigation into Nutrition and Cancer Study2013Ingår i: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 11, nr 11, s. 1486-1492Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer.

    METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire, and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression.

    RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers.

    CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.

  • 20.
    Borgmästars, Emmy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    de Weerd, Hendrik Arnold
    Lubovac-Pilav, Zelmina
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    miRFA: an automated pipeline for microRNA functional analysis with correlation support from TCGA and TCPA expression data in pancreatic cancer2019Ingår i: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 20, artikel-id 393Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: MicroRNAs (miRNAs) are small RNAs that regulate gene expression at a post-transcriptional level and are emerging as potentially important biomarkers for various disease states, including pancreatic cancer. In silico-based functional analysis of miRNAs usually consists of miRNA target prediction and functional enrichment analysis of miRNA targets. Since miRNA target prediction methods generate a large number of false positive target genes, further validation to narrow down interesting candidate miRNA targets is needed. One commonly used method correlates miRNA and mRNA expression to assess the regulatory effect of a particular miRNA.

    The aim of this study was to build a bioinformatics pipeline in R for miRNA functional analysis including correlation analyses between miRNA expression levels and its targets on mRNA and protein expression levels available from the cancer genome atlas (TCGA) and the cancer proteome atlas (TCPA). TCGA-derived expression data of specific mature miRNA isoforms from pancreatic cancer tissue was used.

    Results: Fifteen circulating miRNAs with significantly altered expression levels detected in pancreatic cancer patients were queried separately in the pipeline. The pipeline generated predicted miRNA target genes, enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Predicted miRNA targets were evaluated by correlation analyses between each miRNA and its predicted targets. MiRNA functional analysis in combination with Kaplan-Meier survival analysis suggest that hsa-miR-885-5p could act as a tumor suppressor and should be validated as a potential prognostic biomarker in pancreatic cancer.

    Conclusions: Our miRNA functional analysis (miRFA) pipeline can serve as a valuable tool in biomarker discovery involving mature miRNAs associated with pancreatic cancer and could be developed to cover additional cancer types. Results for all mature miRNAs in TCGA pancreatic adenocarcinoma dataset can be studied and downloaded through a shiny web application at https://emmbor.shinyapps.io/mirfa/.

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  • 21.
    Borgmästars, Emmy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Jacobson, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Simm, Maja
    Johansson, Mattias
    International Agency for Research on Cancer.
    Billing, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Nyström, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Öhlund, Daniel
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lubovac-Pilav, Zelmina
    University of Skövde, Skövde, Sweden.
    Jonsson, Pär
    Franklin, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobankManuskript (preprint) (Övrigt vetenskapligt)
  • 22.
    Borgmästars, Emmy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Jacobson, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Simm, Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Johansson, Mattias
    Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
    Billing, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Nyström, Hanna
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Öhlund, Daniel
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lubovac-Pilav, Zelmina
    Department of Biology and Bioinformatics, University of Skövde, Skövde, Sweden.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Franklin, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, CO, Aurora, United States.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Department of Surgery, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
    Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank2024Ingår i: Journal of Gastrointestinal Oncology, ISSN 2078-6891, E-ISSN 2219-679X, Vol. 15, nr 2, s. 755-767Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.

    Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.

    Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].

    Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.

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  • 23.
    Borgmästars, Emmy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundberg, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Öhlund, Daniel
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nyström, Hanna
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Franklin, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Circulating tissue polypeptide-specific antigen in pre-diagnostic pancreatic cancer samples2021Ingår i: Cancers, ISSN 2072-6694, Vol. 13, nr 21, artikel-id 5321Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging, and late diagnosis partly explains the low 5-year survival. Novel and sensitive biomarkers are needed to enable early PDAC detection and improve patient outcomes. Tissue polypeptide specific antigen (TPS) has been studied as a biomarker in PDAC diagnostics, and it has previously been shown to reflect clinical status better than the ‘golden standard’ biomarker carbohydrate antigen 19-9 (CA 19-9) that is most widely used in the clinical setting. In this cross-sectional case-control study using pre-diagnostic plasma samples, we aim to evaluate the potential of TPS as a biomarker for early PDAC detection. Furthermore, in a subset of individuals with multiple samples available at different time points before diagnosis, a longitudinal analysis was used. We assessed plasma TPS levels using enzyme-linked immunosorbent assay (ELISA) in 267 pre-diagnostic PDAC plasma samples taken up to 18.8 years before clinical PDAC diagnosis and in 320 matched healthy controls. TPS levels were also assessed in 25 samples at PDAC diagnosis. Circulating TPS levels were low both in pre-diagnostic samples of future PDAC patients and in healthy controls, whereas TPS levels at PDAC diagnosis were significantly increased (odds ratio 1.03; 95% confidence interval: 1.01–1.05) in a logistic regression model adjusted for age. In conclusion, TPS levels increase late in PDAC progression and hold no potential as a biomarker for early detection.

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  • 24.
    Borgmästars, Emmy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ulfenborg, Benjamin
    University of Skövde, Skövde, Sweden.
    Johansson, Mattias
    International Agency for Research on Cancer.
    Jonsson, Pär
    Billing, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Franklin, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Lubovac-Pilav, Zelmina
    University of Skövde, Skövde, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Plasma multi-omics in pre-diagnostic pancreatic ductal adenocarcinoma samples from a Swedish prospective biobankManuskript (preprint) (Övrigt vetenskapligt)
  • 25.
    Borgmästars, Emmy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ulfenborg, Benjamin
    School of Bioscience, Department of Biology and Bioinformatics, University of Skövde, Skövde, Sweden.
    Johansson, Mattias
    Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Billing, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Franklin, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, CO, Aurora, United States.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Jacobson, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Simm, Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lubovac-Pilav, Zelmina
    School of Bioscience, Department of Biology and Bioinformatics, University of Skövde, Skövde, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Multi-omics profiling to identify early plasma biomarkers in pre-diagnostic pancreatic ductal adenocarcinoma: a nested case-control study2024Ingår i: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 48, artikel-id 102059Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.

    A nested case-control study within the Northern Sweden Health and Disease Study was designed. Pre-diagnostic plasma samples from 37 future PDAC patients collected within 2.3 years before diagnosis and 37 matched healthy controls were included. We analyzed metabolites using liquid chromatography mass spectrometry and gas chromatography mass spectrometry, microRNAs by HTG edgeseq, proteins by multiplex proximity extension assays, as well as three clinical biomarkers using milliplex technology. Supervised and unsupervised multi-omics integration were performed as well as univariate analyses for the different omics types and clinical biomarkers. Multiple hypothesis testing was corrected using Benjamini-Hochberg's method and a false discovery rate (FDR) below 0.1 was considered statistically significant.

    Carbohydrate antigen (CA) 19-9 was associated with PDAC risk (OR [95 % CI] = 3.09 [1.31–7.29], FDR = 0.03) and increased closer to PDAC diagnosis. Supervised multi-omics models resulted in poor discrimination between future PDAC cases and healthy controls with obtained accuracies between 0.429–0.500. No single metabolite, microRNA, or protein was differentially altered (FDR < 0.1) between future PDAC cases and healthy controls.

    CA 19-9 levels increase up to two years prior to PDAC diagnosis but extensive multi-omics analysis including metabolomics, microRNAomics and proteomics in this cohort did not identify novel early biomarkers for PDAC.

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  • 26. Bremer, T.
    et al.
    Savala, J.
    Leesman, G.
    Wärnberg, F.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Wadsten, Charlotta
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Whitworth, P. W.
    A biologic signature to predict ipsilateral breast event risk at 10 years for early breast cancer2019Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 79, nr 4Artikel i tidskrift (Övrigt vetenskapligt)
  • 27.
    Buchwald, Pamela
    et al.
    Department of Surgery, Skåne University Hospital, Malmö, Sweden; Lund University, Lund, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention. Department of Surgery, Helsinki University, Helsinki, Finland.
    Does it really matter if the surgeon is female or male?2024Ingår i: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 113, nr 2, s. 182-183Artikel i tidskrift (Övrigt vetenskapligt)
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  • 28. Campa, Daniele
    et al.
    Barrdahl, Myrto
    Gaudet, Mia M.
    Black, Amanda
    Chanock, Stephen J.
    Diver, W. Ryan
    Gapstur, Susan M.
    Haiman, Christopher
    Hankinson, Susan
    Hazra, Aditi
    Henderson, Brian
    Hoover, Robert N.
    Hunter, David J.
    Joshi, Amit D.
    Kraft, Peter
    Le Marchand, Loic
    Lindstrom, Sara
    Willett, Walter
    Travis, Ruth C.
    Amiano, Pilar
    Siddiq, Afshan
    Trichopoulos, Dimitrios
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Tjonneland, Anne
    Weiderpass, Elisabete
    Peeters, Petra H.
    Panico, Salvatore
    Dossus, Laure
    Ziegler, Regina G.
    Canzian, Federico
    Kaaks, Rudolf
    Genetic risk variants associated with in situ breast cancer2015Ingår i: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 17, artikel-id 82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS.

    Methods: To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile.

    Results: We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons <0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11-1.38, P = 1.27 x 10(-4)) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99-1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09-1.42, P = 1.07 x 10(-3)). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies.

    Conclusions: Our study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus.

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  • 29. Campa, Daniele
    et al.
    Barrdahl, Myrto
    Tsilidis, Konstantinos K
    Severi, Gianluca
    Diver, W Ryan
    Siddiq, Afshan
    Chanock, Stephen
    Hoover, Robert N
    Ziegler, Regina G
    Berg, Christine D
    Buys, Saundra S
    Haiman, Christopher A
    Henderson, Brian E
    Schumacher, Fredrick R
    Le Marchand, Loic
    Flesch-Janys, Dieter
    Lindstroem, Sara
    Hunter, David J
    Hankinson, Susan E
    Willett, Walter C
    Kraft, Peter
    Cox, David G
    Khaw, Kay-Tee
    Tjonneland, Anne
    Dossus, Laure
    Trichopoulos, Dimitrios
    Panico, Salvatore
    van Gils, Carla H
    Weiderpass, Elisabete
    Barricarte, Aurelio
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Gaudet, Mia M
    Giles, Graham
    Southey, Melissa
    Baglietto, Laura
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Canzian, Federico
    A genome-wide "pleiotropy scan'' does not identify new susceptibility loci for estrogen receptor negative breast cancer2014Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 2, s. e85955-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-). Compared with ER- positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER- negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5x10(-8)) to perform a secondary analysis of an ER- negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER- cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER- GWAS were significant at the adjusted threshold. 186 variants were associated with ER- breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3 x 10(-4). None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a "pleiotropic approach''.

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  • 30. Campa, Daniele
    et al.
    Claus, Rainer
    Dostal, Lucie
    Stein, Angelika
    Chang-Claude, Jenny
    Meidtner, Karina
    Boeing, Heiner
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Rodríguez, Laudina
    Bonet, Catalina
    Sánchez, Maria-José
    Amiano, Pilar
    Huerta, José María
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C
    Allen, Naomi E
    Trichopoulou, Antonia
    Bamia, Christina
    Benetou, Vassiliki
    Palli, Domenico
    Agnoli, Claudia
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    van Kranen, Henk
    Bas Bueno-de-Mesquita, H
    Peeters, Petra H M
    van Gils, Carla H
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lund, Eiliv
    Gram, Inger Torhild
    Rinaldi, Sabina
    Chajes, Veronique
    Romieu, Isabelle
    Engel, Pierre
    Boutron-Ruault, Marie Christine
    Clavel-Chapelon, Françoise
    Siddiq, Afshan
    Riboli, Elio
    Canzian, Federico
    Kaaks, Rudolf
    Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC).2011Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 127, nr 3, s. 761-767Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AMP-activated protein kinase (AMPK) is an energy sensing/signalling intracellular protein which is activated by an increase in the cellular AMP:ATP ratio after ATP depletion. Once activated, AMPK inhibits fatty acid synthesis and the Akt-mTOR pathway, and activates the p53-p21 axis. All these molecular mechanisms are thought to play a key role in breast carcinogenesis. We investigated the genetic variability of four genes encoding AMPK (PRKAA1, PRKAA2, PRKAB1 and PRKAB2). Using a tagging approach and selecting SNPs we covered all the common genetic variation of these genes. We tested association of tagging SNPs in our four candidate genes with breast cancer (BC) risk in a study of 1340 BC cases and 2536 controls nested into the European Prospective Investigation into Cancer and Nutrition (EPIC). Given the relevance of AMPK on fatty acid synthesis and the importance of body fatness as a BC risk factor, we tested association of SNPs and body-mass index as well. We observed no statistically significant association between the SNPs in the PRKAs genes and BC risk and BMI after correction for multiple testing.

  • 31. Campa, Daniele
    et al.
    Mergarten, Bjoern
    De Vivo, Immaculata
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Severi, Gianluca
    Nieters, Alexandra
    Katzke, Verena A.
    Trichopoulou, Antonia
    Yiannakouris, Nikos
    Trichopoulos, Dimitrios
    Boeing, Heiner
    Ramon Quiros, J.
    Duell, Eric J.
    Molina-Montes, Esther
    Mara Huerta, Jose
    Ardanaz, Eva
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C.
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Vineis, Paolo
    Riboli, Elio
    Siddiq, Afshan
    Bueno-de-Mesquita, H. B.
    Peeters, Petra H.
    Nilsson, Peter M.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ye, Weimin
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Karolinska Inst, Dept Med Epidemiol & Biostat.
    Lund, Eiliv
    Jareid, Mie
    Weiderpass, Elisabete
    Duarte-Salles, Talita
    Kong, So Yeon
    Stepien, Magdalena
    Canzian, Federico
    Kaaks, Rudolf
    Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study2014Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, nr 11, s. 2447-2454Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. Methods: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). Results: We observed that the mean LTL was higher in cases (0.59 +/- 0.20) than in controls (0.57 +/- 0.17), although this difference was not statistically significant (P = 0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk [OR, 1.13; 95% confidence interval (CI), 1.01-1.27]. Additional analyses by cubic spline regression suggested a possible nonlinear relationship between LTL and pancreatic cancer risk (P = 0.022), with a statistically nonsignificant increase in risk at very low LTL, as well as a significant increase at high LTL. Conclusion: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. Impact: The results of this article can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk.

  • 32.
    Castro-Espin, Carlota
    et al.
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain.
    Bonet, Catalina
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain.
    Crous-Bou, Marta
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States.
    Katzke, Verena
    German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Le Cornet, Charlotte
    German Institute of Human Nutrition Potsdam-Rehbruecke, Dept. of Molecular Epidemiology, Arthur-Scheunert-Allee, Nuthetal, Germany.
    Jannasch, Franziska
    German Institute of Human Nutrition Potsdam-Rehbruecke, Dept. of Molecular Epidemiology, Arthur-Scheunert-Allee, Nuthetal, Germany.
    Schulze, Matthias B.
    German Institute of Human Nutrition Potsdam-Rehbruecke, Dept. of Molecular Epidemiology, Arthur-Scheunert-Allee, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Olsen, Anja
    Danish Cancer Society Research Center, Diet, Cancer and Health, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Diet, Cancer and Health, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Antoniussen, Christian S.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Sánchez, Maria Jose
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Amiano, Pilar
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain.
    Chirlaque, María Dolores
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Guevara, Marcela
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Tumino, Rosario
    Hyblean Association for Epidemiological Research, AIRE ONLUS Ragusa, Ragusa, Italy.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, Turin, Italy.
    De Magistris, Maria Santucci
    A.O.U. Federico II, Naples, Italy.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Bodén, Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jensen, Torill Enget
    Department of Community Medicine, UiT the Arctic University of Norway, Tromsø, Norway.
    Olsen, Karina Standahl
    Department of Community Medicine, UiT the Arctic University of Norway, Tromsø, Norway.
    Skeie, Guri
    Department of Community Medicine, UiT the Arctic University of Norway, Tromsø, Norway.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Rinaldi, Sabina
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Gonzalez-Gil, Esther M.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Weiderpass, Elisabete
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Christakoudi, Sofia
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Inflammation Biology, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom.
    Heath, Alicia K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Dossus, Laure
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Agudo, Antonio
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain.
    Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis: results from a cohort study2023Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 128, s. 1301-1310Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Inflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival.

    Methods: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality.

    Results: We included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1–SD 0.92; 95%CI 0.87–0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1–SD 1.06; 95%CI 1.00–1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality.

    Conclusions: Greater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.

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  • 33.
    Castro-Espin, Carlota
    et al.
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain.
    Bonet, Catalina
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain.
    Crous-Bou, Marta
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States.
    Nadal-Zaragoza, Núria
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain.
    Tjønneland, Anne
    The Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, The University of Copenhagen, Copenhagen, Denmark.
    Mellemkjær, Lene
    The Danish Cancer Society Research Center, Copenhagen, Denmark.
    Hajji-Louati, Mariem
    Université Paris-Saclay, UVSQ, Inserm “Exposome, Heredity, Cancer and Health” Team, CESP U1018, Gustave Roussy, Villejuif, France.
    Truong, Thérèse
    Université Paris-Saclay, UVSQ, Inserm “Exposome, Heredity, Cancer and Health” Team, CESP U1018, Gustave Roussy, Villejuif, France.
    Katzke, Verena
    German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Le Cornet, Charlotte
    German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Jannasch, Franziska
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
    Masala, Giovanna
    Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
    Sieri, Sabina
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Via Venezian, 1. 20133, Milan, Italy.
    Panico, Salvatore
    Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
    Di Girolamo, Chiara
    Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, TO, Orbassano, Italy.
    Skeie, Guri
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Borch, Kristin Benjaminsen
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Olsen, Karina Standahl
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Sánchez, Maria-Jose
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Amiano, Pilar
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastian, Spain.
    Chirlaque, María-Dolores
    Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Guevara, Marcela
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Department of Surgery, University of Helsinki & Helsinki University Hospital, Helsinki, Finland.
    Bodén, Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Gunter, Marc J.
    International Agency for Research on Cancer, World Health Organization, Lyon, France; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Gonzalez-Gil, Esther M.
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Aguilera-Buenosvinos, Inmaculada
    Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; International Agency for Research on Cancer, World Health Organization, Lyon, France; Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
    Tsilidis, Kostas K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Heath, Alicia K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Aune, Dagfinn
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Nutrition, Oslo New University College, Oslo, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital Ullevål, Oslo, Norway.
    Dossus, Laure
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Agudo, Antonio
    Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain.
    Association of Mediterranean diet with survival after breast cancer diagnosis in women from nine European countries: results from the EPIC cohort study2023Ingår i: BMC Medicine, E-ISSN 1741-7015, Vol. 21, nr 1, artikel-id 225Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The Mediterranean diet has been associated with lower risk of breast cancer (BC) but evidence from prospective studies on the role of Mediterranean diet on BC survival remains sparse and conflicting. We aimed to investigate whether adherence to Mediterranean diet prior to diagnosis is associated with overall and BC-specific mortality.

    Methods: A total of 13,270 incident breast cancer cases were identified from an initial sample of 318,686 women in 9 countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to Mediterranean diet was estimated through the adapted relative Mediterranean diet (arMED), a 16-point score that includes 8 key components of the Mediterranean diet and excludes alcohol. The degree of adherence to arMED was classified as low (score 0–5), medium (score 6–8), and high (score 9–16). Multivariable Cox proportional hazards models were used to analyze the association between the arMED score and overall mortality, and Fine-Gray competing risks models were applied for BC-specific mortality.

    Results: After a mean follow-up of 8.6 years from diagnosis, 2340 women died, including 1475 from breast cancer. Among all BC survivors, low compared to medium adherence to arMED score was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95%CI 1.01–1.26). High compared to medium adherence to arMED showed a non-statistically significant association (HR 0.94; 95% CI 0.84–1.05). With no statistically significant departures from linearity, on a continuous scale, a 3-unit increase in the arMED score was associated with an 8% reduced risk of overall mortality (HR3-unit 0.92, 95% CI: 0.87–0.97). This result sustained when restricted to postmenopausal women and was stronger among metastatic BC cases (HR3-unit 0.81, 95% CI: 0.72–0.91).

    Conclusions: Consuming a Mediterranean diet before BC diagnosis may improve long-term prognosis, particularly after menopause and in cases of metastatic breast cancer. Well-designed dietary interventions are needed to confirm these findings and define specific dietary recommendations.

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  • 34.
    Charvat, Hadrien
    et al.
    Cancer Surveillance Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
    Freisling, Heinz
    Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
    Noh, Hwayoung
    Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
    Gaudet, Mia M.
    Department of Population Sciences, American Cancer Society, GA, Atlanta, United States.
    Gunter, Marc J.
    Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Bergmann, Manuela
    Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrucke, Nuthetal, Germany.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Rylander, Charlotta
    Department of Community Medicine, Faculty of Health Sciences, University of Tromsø (UiT), The Arctic University of Norway, Tromsø, Norway.
    Skeie, Guri
    Department of Community Medicine, Faculty of Health Sciences, University of Tromsø (UiT), The Arctic University of Norway, Tromsø, Norway; Nutritional Epidemiology Group, School of Food and Nutrition, University of Leeds, Leeds, United Kingdom.
    Jakszyn, Paula
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain; Facultat Ciències Salut Blanquerna, Universitat Ramon Llull, Barcelona, Spain.
    Rosendahl, Ann H.
    Department of Clinical Sciences Lund, Oncology, Lund University, Skå ne University Hospital, Lund, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Severi, Gianluca
    Center for Research in Epidemiology and Population Health, Institut Gustave Roussy, Villejuif, France.
    Tsugane, Shoichiro
    Epi-demiology and Prevention Division, National Cancer Center, Tokyo, Japan.
    Sawada, Norie
    Epi-demiology and Prevention Division, National Cancer Center, Tokyo, Japan.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Adami, Hans-Olov
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo, Norway.
    Weiderpass, Elisabete
    Director’s Office, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
    Soerjomataram, Isabelle
    Cancer Surveillance Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
    Arnold, Melina
    Cancer Surveillance Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
    Excess body fatness during early to mid-adulthood and survival from colorectal and breast cancer: a pooled analysis of five international cohort studies2022Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 31, nr 2, s. 325-333Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries.

    Methods: Participant-level body mass index (BMI) trajectories were estimated by fitting a growth curve model using over 2 million repeated BMI measurements from close to 600,000 cohort participants. Cumulative measures of excess weight were derived. Data from over 23,000 patients with breast and colorectal cancer were subsequently analyzed using time-to-event models for death with the date of diagnosis as start of follow-up. Study-specific results were combined through a random effect meta-analysis.

    Results: We found a significant dose–response relationship (P trend ¼ 0.013) between the average BMI during early and mid-adulthood and death from breast cancer, with a pooled HR of 1.31 (1.07–1.60) and the time to death shortened by 16% for average BMI above 25 kg/m2 compared with average BMI less than or equal to 22.5 kg/m2, respectively. Similar results were found for categories of cumulative time spent with excess weight. There was no association between excess body fatness during early to mid-adulthood and death in patients with colorectal cancer.

    Conclusions: Excess body fatness during early to mid-adulthood is associated not only with an increased risk of developing cancer, but also with a lower survival in patients with breast cancer.

    Impact: Our results emphasize the importance of public health policies aimed at reducing overweight during adulthood and inform future studies on the relationship between excess weight and cancer outcomes.

  • 35. Chuang, Shu-Chun
    et al.
    Stolzenberg-Solomon, Rachael
    Ueland, Per Magne
    Vollset, Stein Emil
    Midttun, Oivind
    Olsen, Anja
    Tjonneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Clavel-Chapelon, Francoise
    Teucher, Birgit
    Kaaks, Rudolf
    Weikert, Cornelia
    Boeing, Heiner
    Trichopoulou, Antonia
    Benetou, Vassiliki
    Naska, Androniki
    Jenab, Mazda
    Slimani, Nadia
    Romieu, Isabelle
    Michaud, Dominique S.
    Palli, Domenico
    Sieri, Sabina
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Skeie, Guri
    Duell, Eric J.
    Rodriguez, Laudina
    Molina-Montes, Esther
    Maria Huerta, Jose
    Larranaga, Nerea
    Barricarte Gurrea, Aurelio
    Johansen, Dorthe
    Manjer, Jonas
    Ye, Weimin
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Peeters, Petra H. M.
    Jeurnink, Suzanne
    Wareham, Nicholas
    Khaw, Kay-Tee
    Crowe, Francesca
    Riboli, Elio
    Bueno-de-Mesquita, Bas
    Vineis, Paolo
    A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition2011Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, nr 12, s. 1808-1816Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/- 1 year), date (+/- 1 year) and time (+/- 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate <= 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI = 0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR = 1.17, 95% CI = 1.00-1.38) but not in women (OR = 0.91, 95% CI = 0.78-1.07; p for heterogeneity < 0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.

  • 36. Cirera, Lluís
    et al.
    Huerta, José María
    Chirlaque, María Dolores
    Overvad, Kim
    Lindström, Martin
    Regnér, Sara
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Rebours, Vinciane
    Fagherazzi, Guy
    Katzke, Verena A.
    Boeing, Heiner
    Peppa, Eleni
    Trichopoulou, Antonia
    Valanou, Elissavet
    Palli, Domenico
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    van Gils, Carla
    Vermeulen, Roel C. H.
    Skeie, Guri
    Braaten, Tonje
    Weiderpass, Elisabete
    Merino, Susana
    Sánchez, María José
    Larrañaga, Nerea
    Ardanaz, Eva
    Sund, Malin
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Khaw, Kay-Tee
    Key, Timothy J.
    Jenab, Mazda
    Naudin, Sabine
    Murphy, Neil
    Aune, Dagfinn
    Ward, Heather
    Riboli, Elio
    Bueno-de-Mesquita, Bas
    Navarro, Carmen
    Duell, Eric J.
    Socioeconomic Effect of Education on Pancreatic Cancer Risk in Western Europe: An Update on the EPIC Cohorts Study2019Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, nr 6, s. 1089-1092Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up.

    METHODS: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors.

    RESULTS: A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02-1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05-1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance.

    CONCLUSIONS: The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems.

    IMPACT: The results do not support an association between education and risk of pancreatic cancer.

  • 37.
    Clendenen, Tess V.
    et al.
    Department of Population Health, New York University School of Medicine, NY, New York, United States.
    Ge, Wenzhen
    Department of Population Health, New York University School of Medicine, NY, New York, United States.
    Koenig, Karen L.
    Department of Population Health, New York University School of Medicine, NY, New York, United States.
    Afanasyeva, Yelena
    Department of Population Health, New York University School of Medicine, NY, New York, United States.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
    Bertone-Johnson, Elizabeth
    Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, MA, Amherst, United States.
    Brinton, Louise A.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Darvishian, Farbod
    Pathology, New York University School of Medicine, NY, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, NY, New York, United States.
    Dorgan, Joanne F.
    Department of Epidemiology and Public Health, University of Maryland School of Medicine, MD, Baltimore, United States.
    Eliassen, A. Heather
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States.
    Falk, Roni T.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hankinson, Susan E.
    Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, MA, Amherst, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States.
    Hoffman-Bolton, Judith
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Key, Timothy J.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Krogh, Vittorio
    Epidemiology and Prevention Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
    Nichols, Hazel B.
    Department of Epidemiology, University of North Carolina, NC, Chapel Hill, United States.
    Sandler, Dale P.
    Epidemiology Branch, National Institute of Environmental Health Sciences, NC, Research Triangle Park, United States.
    Schoemaker, Minouk J.
    Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
    Sluss, Patrick M.
    Department of Pathology, Harvard Medical School, MA, Boston, United States.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Department of Surgery, Umeå University Hospital, Umeå, Sweden.
    Swerdlow, Anthony J.
    Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom; Division of Breast Cancer Research, The Institute of Cancer Research, London, United Kingdom.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States; Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, MD, Baltimore, United States.
    Liu, Mengling
    Department of Population Health, New York University School of Medicine, NY, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, NY, New York, United States.
    Zeleniuch-Jacquotte, Anne
    Department of Population Health, New York University School of Medicine, NY, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, NY, New York, United States.
    Breast Cancer Risk Factors and Circulating Anti-Müllerian Hormone Concentration in Healthy Premenopausal Women2021Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, nr 11, s. E4542-E4553Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: We previously reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies.

    Objective: This study assessed whether risk factors for breast cancer are correlates of AMH concentration.

    Methods: This cross-sectional study included 3831 healthy premenopausal women (aged 21-57, 87% aged 35-49) from 10 cohort studies among the general population.

    Results: Adjusting for age and cohort, AMH positively associated with age at menarche (P < 0.0001) and parity (P = 0.0008) and inversely associated with hysterectomy/partial oophorectomy (P = 0.0008). Compared with women of normal weight, AMH was lower (relative geometric mean difference 27%, P < 0.0001) among women who were obese. Current oral contraceptive (OC) use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, P < 0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, P = 0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40 vs ≥40), associations of AMH with body mass index and OCs were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (P-interaction < 0.05).

    Conclusion: This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and it suggests that most associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.

  • 38. Clendenen, Tess V.
    et al.
    Ge, Wenzhen
    Koenig, Karen L.
    Axelsson, Tomas
    Liu, Mengling
    Afanasyeva, Yelena
    Andersson, Anne
    Arslan, Alan A.
    Chen, Yu
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lenner, Per
    Kirchhoff, Tomas
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Shore, Roy E.
    Sund, Malin
    Zeleniuch-Jacquotte, Anne
    Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: a nested case-control study2015Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 10, nr 10, artikel-id e0140478Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH) D concentration in GWAS were also associated with plasma 25(OH) D in our study (p-trend < 0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH) D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.

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  • 39. Companioni, Osmel
    et al.
    Bonet, Catalina
    Muñoz, Xavier
    Weiderpass, Elisabete
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Agnoli, Claudia
    Vineis, Paolo
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Clavel-Chapelon, Françoise
    Travis, Ruth C
    Khaw, Kay-Tee
    Riboli, Elio
    Murphy, Neil
    Vergnaud, Anne-Claire
    Trichopoulou, Antonia
    Benetou, Vassiliki
    Trichopoulos, Dimitrios
    Lund, Eiliv
    Johansen, Dorthe
    Lindkvist, Björn
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ardanaz, Eva
    Sánchez-Cantalejo, Emilio
    Huerta, Jose M
    Dorronsoro, Miren
    Quirós, José Ramón
    Tjonneland, Anne
    Mortensen, Lotte Maxild
    Overvad, Kim
    Chang-Claude, Jenny
    Rizzato, Cosmeri
    Boeing, Heiner
    de Mesquita, H Bas Bueno
    Siersema, Peter
    Peeters, Petra Hm
    Numans, Mattijs E
    Carneiro, Fatima
    Licaj, Idlir
    Freisling, Heinz
    Sala, Núria
    González, Carlos A
    Polymorphisms of H. pylori signaling pathway genes and gastric cancer risk in the European EPIC-eurgast cohort2014Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, nr 1, s. 92-101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccaride and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. SNPs in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1284 matched controls from the EPIC cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p=0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p=0.0003) and CD14 with cardia GC (p=0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.

  • 40. COVIDSurg Collaborative,
    Löfgren, N. (Medarbetare/bidragsgivare)
    Umea University Hospital.
    Rutegård, Martin (Medarbetare/bidragsgivare)
    Umea University Hospital.
    Sund, Malin (Medarbetare/bidragsgivare)
    Umea University Hospital.
    Delaying surgery for patients with a previous SARS-CoV-2 infection2020Ingår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 107, nr 12, s. e601-e602Artikel i tidskrift (Refereegranskat)
  • 41. De Boniface, J.
    et al.
    Ahlgren, J.
    Andersson, Y.
    Bergkvist, L.
    Frisell, J.
    Lundstedt, D.
    Bagge, R. Olofsson
    Ryden, L.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    The generalisability of randomised clinical trials: An interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer2020Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 138, s. S3-S3Artikel i tidskrift (Övrigt vetenskapligt)
  • 42.
    de Boniface, J.
    et al.
    Departments of Molecular Medicine and Surgery, Sweden; Department of Surgery, Capio St. Göran’s Hospital,, Sweden.
    Tvedskov, T. Filtenborg
    Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Breast Surgery, Gentofte Hospital, Denmark.
    Rydén, L.
    Faculty of Medicine, Institute of Clinical Sciences, Lund University, Sweden.
    Szulkin, R.
    Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden; Department of Surgery, Capio St. Göran’s Hospital,, Sweden.
    Reimer, T.
    Department of Obstetrics and Gynecology, University of Rostock, Rostock Breast Center, Die Filderklinik, Germany.
    Kühn, T.
    Department of Obstetrics and Gynecology, University of Rostock, Rostock Breast Center, Die Filderklinik, Germany; Department of Gynecology and Obstetrics, University of Ulm, Germany.
    Kontos, M.
    First Department of Surgery, National and Kapodistrian University of Athens, Greece.
    Gentilini, O.D.
    Department of Breast Surgery, IRCCS Ospedale San Raffaele, Italy; Vita-Salute San Raffaele University,, Italy.
    Bagge, R. Olofsson
    Skåne University Hospital Lund, Sweden; Departments of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Departments of Surgery, Sahlgrenska University Hospital, Sweden; Department of Surgery, University of Helsinki and Helsinki University Hospital, Italy.
    Lundstedt, D.
    Departments of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Sweden; Departments of Oncology, Sahlgrenska University Hospital, Sweden.
    Appelgren, M.
    Departments of Molecular Medicine and Surgery, Sweden; Department of Surgery, Capio St. Göran’s Hospital,, Sweden.
    Ahlgren, J.
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Sweden; Regional Cancer Center of Mid-Sweden, Sweden.
    Norenstedt, S.
    Departments of Molecular Medicine and Surgery, Sweden; Department of Surgery, Capio St. Göran’s Hospital,, Sweden.
    Celebioglu, F.
    Department of Surgery, Sweden.
    Sackey, H.
    Breast Center Karolinska, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Sweden.
    Andersen, I. Scheel
    Department of Surgery, Breast Clinic, Viborg Hospital, Denmark.
    Hoyer, U.
    Department of Plastic and Breast Surgery, Aalborg University Hospital, Denmark.
    Nyman, P.F.
    Department of Surgery, Skaraborg Hospital, Sweden.
    Patil, E. Vikhe
    Linköping University, and the Department of Surgery, Linköping University Hospital, Linköping, Sweden.
    Wieslander, E.
    Radiation Physics, Department of Hematology, Oncology, and Radiation Physics, Sweden.
    Nissen, H. Dahl
    Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Denmark.
    Alkner, S.
    Faculty of Medicine, Institute of Clinical Sciences, Lund University, Sweden; Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital Lund, Sweden.
    Andersson, Y.
    Center for Clinical Research, Uppsala University and Region Vastmanland, Vastmanland Hospital, Sweden.
    Offersen, B.V.
    Departments of Oncology and Plastic and Breast Surgery, Denmark; University Hospital, the Departments of Oncology, Denmark; Department of Experimental Clinical Oncology, Danish Center for Particle Therapy, Denmark.
    Bergkvist, L.
    Center for Clinical Research, Uppsala University and Region Vastmanland, Vastmanland Hospital, Sweden.
    Frisell, J.
    Breast Center Karolinska, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Sweden.
    Christiansen, P.
    Departments of Oncology and Plastic and Breast Surgery, Denmark; Clinical Medicine, Aarhus University, Denmark.
    Omitting axillary dissection in breast cancer with sentinel-node metastases2024Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 390, nr 13, s. 1163-1175Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups.

    METHODS We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44.

    RESULTS Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy–only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy–only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin.

    CONCLUSIONS The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).

  • 43. de Boniface, Jana
    et al.
    Ahlgren, Johan
    Andersson, Yvette
    Bergkvist, Leif
    Frisell, Jan
    Lundstedt, Dan
    Olofsson Bagge, Roger
    Rydén, Lisa
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Surgery Center, Norrland University Hospital, Umeå, Sweden.
    The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer2020Ingår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 180, nr 1, s. 167-176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC).

    METHODS: In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1-T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years.

    RESULTS: Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time.

    CONCLUSIONS: This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials.

    TRIAL REGISTRATION: NCT02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.

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  • 44. de Boniface, Jana
    et al.
    Frisell, Jan
    Andersson, Yvette
    Bergkvist, Leif
    Ahlgren, Johan
    Ryden, Lisa
    Bagge, Roger Olofsson
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Surgery Center, Norrland University Hospital, Umeå, Sweden.
    Johansson, Hemming
    Lundstedt, Dan
    Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial2017Ingår i: BMC Cancer, E-ISSN 1471-2407, Vol. 17, artikel-id 379Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.

    Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1:1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.

    Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.

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  • 45. Del Chiaro, Marco
    et al.
    Besselink, Marc G.
    Scholten, Lianne
    Bruno, Marco J.
    Cahen, Djuna L.
    Gress, Thomas M.
    van Hooft, Jeanin E.
    Lerch, Markus M.
    Mayerle, Julia
    Hackert, Thilo
    Satoi, Sohei
    Zerbi, Alessandro
    Cunningham, David
    De Angelis, Claudio
    Giovanni, Marc
    de-Madaria, Enrique
    Hegyi, Peter
    Rosendahl, Jonas
    Friess, Helmut
    Manfredi, Riccardo
    Levy, Philippe
    Real, Francisco X.
    Sauvanet, Alain
    Abu Hilal, Mohammed
    Marchegiani, Giovanni
    Esposito, Irene
    Ghaneh, Paula
    Engelbrecht, Marc R. W.
    Fockens, Paul
    van Huijgevoort, Nadine C. M.
    Wolfgang, Christopher
    Bassi, Claudio
    Gubergrits, Natalya B.
    Verbeke, Caroline
    Kloppel, Gunter
    Scarpa, Aldo
    Zamboni, Giuseppe
    Lennon, Anne Marie
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Kartalis, Nikolaos
    Grenacher, Lars
    Falconi, Massimo
    Arnelo, Urban
    Kopchak, Kostantin V.
    Oppong, Kofi
    McKay, Colin
    Hauge, Truls
    Conlon, Kevin
    Adham, Mustapha
    Ceyhan, Guralp O.
    Salvia, Roberto
    Dervenis, Christos
    Allen, Peter
    Paye, Francois
    Bartsch, Detlef K.
    Lohr, Matthias
    Mutignani, Massimiliano
    Laukkarinen, Johanna
    Schulick, Richard
    Valente, Roberto
    Seufferlein, Thomas
    Capurso, Gabriele
    Siriwardena, Ajith
    Neoptolemos, John P.
    Pukitis, Aldis
    Segersvard, Ralf
    Aghdassi, A.
    Andrianello, S.
    Bossuyt, P.
    Bulow, R.
    Cardenas-Jaen, K.
    Cortegoso, P.
    Fontana, M.
    Haeberle, L.
    Heckler, M.
    Litvin, A.
    Mann, K.
    Michalski, C.
    Michl, P.
    Nappo, G.
    Perri, G.
    Persson, S.
    Scheufele, F.
    Sclafani, F.
    Schmidt, M.
    Venezia, L.
    Volker, F.
    Vullierm, M-P
    Wusten, L.
    European evidence-based guidelines on pancreatic cystic neoplasms2018Ingår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, nr 5, s. 789-804Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring < 40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter >= 40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule > 5 mm, and MPD diameter > 10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

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  • 46.
    Devarajan, Raman
    et al.
    Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine; Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland.
    Izzi, Valerio
    Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Research Unit of Biomedicine, University of Oulu, Oulu, Finland; Finnish Cancer Research Institute, Helsinki, Finland.
    Peltoketo, Hellevi
    Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland.
    Rask, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Kauppila, Saila
    Department of Pathology, Oulu University Hospital and University of Oulu, Oulu, Finland; Northern Finland Laboratory Centre, NordLab, Oulu, Finland.
    Väisänen, Marja-Riitta
    Department of Pathology, Kainuu Central Hospital, Kajaani, Finland.
    Ruotsalainen, Heli
    Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
    Martínez-Nieto, Guillermo
    Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
    Karppinen, Sanna-Maria
    Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
    Väisänen, Timo
    Department of Pathology, Oulu University Hospital and University of Oulu, Oulu, Finland.
    Kaur, Inderjeet
    Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
    Koivunen, Jussi
    Department of Medical Oncology and Radiotherapy and Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
    Sasaki, Takako
    Department of Pharmacology, Faculty of Medicine, Oita University, Oita, Japan.
    Winqvist, Robert
    Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit; Biocenter Oulu, University of Oulu, Oulu, Finland; Northern Finland Laboratory Centre, NordLab, Oulu, Finland.
    Manninen, Aki
    Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
    Wärnberg, Fredrik
    Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Pihlajaniemi, Taina
    Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
    Heljasvaara, Ritva
    Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
    Targeting collagen XVIII improves the efficiency of ErbB inhibitors in breast cancer models2023Ingår i: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 133, nr 18, artikel-id e159181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The tumor extracellular matrix (ECM) critically regulates cancer progression and treatment response. Expression of the basement membrane component collagen XVIII (ColXVIII) is induced in solid tumors, but its involvement in tumorigenesis has remained elusive. We show here that ColXVIII was markedly upregulated in human breast cancer (BC) and was closely associated with a poor prognosis in high-grade BCs. We discovered a role for ColXVIII as a modulator of epidermal growth factor receptor tyrosine kinase (ErbB) signaling and show that it forms a complex with ErbB1 and -2 (also known as EGFR and human epidermal growth factor receptor 2 [HER2]) and α6-integrin to promote cancer cell proliferation in a pathway involving its N-terminal portion and the MAPK/ERK1/2 and PI3K/AKT cascades. Studies using Col18a1 mouse models crossed with the mouse mammary tumor virus-polyoma virus middle T antigen (MMTV-PyMT) mammary carcinogenesis model showed that ColXVIII promoted BC growth and metastasis in a tumor cell-autonomous manner. Moreover, the number of mammary cancer stem cells was significantly reduced in the MMTV-PyMT and human cell models upon ColXVIII inhibition. Finally, ablation of ColXVIII substantially improved the efficacy of ErbB-targeting therapies in both preclinical models. In summary, ColXVIII was found to sustain the stemness properties of BC cells and tumor progression and metastasis through ErbB signaling, suggesting that targeting ColXVIII in the tumor milieu may have important therapeutic potential.

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  • 47.
    Dimberg, A.
    et al.
    Uppsala University, Uppsala, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Cancer angiogenesis and vasculogenesis2014Ingår i: Pathobiology of human disease: a dynamic encyclopedia of disease mechanisms / [ed] Linda M. McManus; Richard N. Mitchell, Academic Press, 2014, s. 403-411Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    A growing tumor is dependent on developing a functioning vasculature. Blood vessels can be formed through de novo differentiation from endothelial progenitor cells in the process of vasculogenesis or by sprouting or splitting from existing blood vessels in the process of angiogenesis. In this article, these processes are discussed in detail with a special focus on the signaling events that guide the development of a tumor vasculature. Preventing angiogenesis is a potential way of treating cancer, and many antiangiogenic substances have entered the clinic and are used as therapeutic options for certain cancers.

  • 48. Duell, Eric J.
    et al.
    Travier, Noemie
    Lujan-Barroso, Leila
    Dossus, Laure
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Tumino, Rosario
    Masala, Giovanna
    Krogh, Vittorio
    Panico, Salvatore
    Ricceri, Fulvio
    Luisa Redondo, Maria
    Dorronsoro, Miren
    Molina-Montes, Esther
    Huerta, Jose M.
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick J.
    Allen, Naomi E.
    Travis, Ruth
    Siersema, Peter D.
    Peeters, Petra H. M.
    Trichopoulou, Antonia
    Fragogeorgi, Eirini
    Oikonomou, Eleni
    Boeing, Heiner
    Schuetze, Madlen
    Canzian, Federico
    Lukanova, Annekatrin
    Tjonneland, Anne
    Roswall, Nina
    Overvad, Kim
    Weiderpass, Elisabete
    Gram, Inger Torhild
    Lund, Eiliv
    Lindkvist, Bjorn
    Johansen, Dorthe
    Ye, Weimin
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Fedirko, Veronika
    Jenab, Mazda
    Michaud, Dominique S.
    Riboli, Elio
    Bueno-de-Mesquita, H. Bas
    Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort2013Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, nr 9, s. 2164-2175Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.992.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort.

  • 49. Ekelund, Ulf
    et al.
    Ward, Heather A.
    Norat, Teresa
    Luan, Jian'an
    May, Anne M.
    Weiderpass, Elisabete
    Sharp, Stephen J.
    Overvad, Kim
    Ostergaard, Jane Nautrup
    TjOnneland, Anne
    Johnsen, Nina Fons
    Mesrine, Sylvie
    Foamier, Agnes
    Fagherazzi, Guy
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Li, Kuanrong
    Kaaks, Rudolf
    Ferrari, Pietro
    Licaj, Idlir
    Jenab, Mazda
    Bergmann, Manuela
    Boeing, Heiner
    Palli, Domenico
    Sieri, Sabina
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H.
    Monnikhof, Evelyn
    Bueno-de-Mesquita, H. Bas
    Ramon Quiros, J.
    Agudo, Antonio
    Sanchez, Maria-Jose
    Maria Huerta, Jose
    Ardanaz, Eva
    Arriola, Larraitz
    Hedblad, Bo
    Wirfalt, Elisabet
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. International Agency for Research on Cancer (IARC), Lyon, France.
    Key, Timothy J.
    Travis, Ruth C.
    Khaw, Kay-Tee
    Brage, Soren
    Wareham, Nicholas J.
    Riboli, Elio
    Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC)2015Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 101, nr 3, s. 613-621Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear.

    Objective: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures.

    Design: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (>= 102 cm for men, >= 88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures.

    Results: Significant interactions (PA x BMI and PA x WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity.

    Conclusion: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.

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  • 50. Ellingjord-Dale, Merete
    et al.
    Christakoudi, Sofia
    Weiderpass, Elisabete
    Panico, Salvatore
    Dossus, Laure
    Olsen, Anja
    Tjønneland, Anne
    Kaaks, Rudolf
    Schulze, Matthias B.
    Masala, Giovanna
    Gram, Inger T.
    Skeie, Guri
    Rosendahl, Ann H.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Key, Tim
    Ferrari, Pietro
    Gunter, Marc
    Heath, Alicia K.
    Tsilidis, Konstantinos K.
    Riboli, Elio
    Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2022Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 50, nr 6, s. 1914-1926Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status.

    METHODS: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer.

    RESULTS: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (±2.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% confidence interval 1.22-1.65] in ever HRT users (HR = 1.23; 1.04-1.44), in never HRT users (HR = 1.40; 1.16-1.68) and in oestrogen-and-progesterone-receptor-positive (ER+PR+) breast cancer (HR = 1.46; 1.15-1.85).

    CONCLUSION: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer.

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