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Metabolic factors and risk of prostate, kidney, and bladder cancer
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Prostate cancer is the most common cancer in Sweden with around 10,000 new cases every year. Kidney and bladder cancer are less common with 1,000 and 2,000 new cases annually, respectively. The incidence of these cancer sites is higher in developed, than in developing countries, suggesting an association between lifestyle and cancer risk. The aims of this thesis were to investigate body mass index (BMI), blood pressure, and blood levels of glucose, total cholesterol, and triglycerides as risk factors for prostate, kidney, and bladder cancer. Furthermore, we aimed at assess probabilities of prostate cancer and competing events, all-cause death, for men with normal and high levels of metabolic factors.

Material and methods: This thesis was conducted within the Metabolic Syndrome and Cancer project (Me-Can), a pooled cohort study with data from 578,700 participants from Norway, Sweden, and Austria. Data from metabolic factors were prospectively collected at health examinations and linked to the Cancer and Cause of Death registers in each country. 

Results: High levels of metabolic factors were not associated with increased risk of prostate cancer, but high levels of BMI and blood pressure were associated with risk of prostate cancer death. The probability of prostate cancer was higher for men with normal levels of metabolic factors compared to men with high levels, but the probability of all-cause death, was higher for men with high levels than for those with normal levels. For both men and women, high levels of metabolic factors were associated with increased risk of kidney cancer (renal cell carcinoma). Furthermore, blood pressure for men and BMI for women were found as independent risk factors of kidney cancer. High blood pressure was associated with an increased risk of bladder cancer for men.

Conclusions: High levels of metabolic factors were associated to risk of kidney and bladder cancer and to death from kidney, bladder, and prostate cancer. Compared to men with normal levels, men with high levels of metabolic factors had a decreased probability of prostate cancer but an increased probability of all-cause death.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2013. , 58 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1612
Keyword [en]
cohort study, competing risk, epidemiology, metabolic factors, prostate cancer, kidney cancer, bladder cancer, renal cell carcinoma, survival analysis
National Category
Urology and Nephrology
Research subject
Epidemiology; Urology; Oncology
Identifiers
URN: urn:nbn:se:umu:diva-83947ISBN: 978-91-7459-763-9 (print)OAI: oai:DiVA.org:umu-83947DiVA: diva2:678047
Public defence
2014-01-24, Hörsal E04, byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Projects
Me-Can
Funder
Swedish Cancer Society, 2010/628
Note

Ytterligare forskningsfinansiärer: World Cancer Research Fund (2007/09) och Wereld Kanker Onderzoek Fonds (R2010/247)

Available from: 2013-12-17 Created: 2013-12-11 Last updated: 2014-01-15Bibliographically approved
List of papers
1. Prospective study on metabolic factors and risk of prostate cancer
Open this publication in new window or tab >>Prospective study on metabolic factors and risk of prostate cancer
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2012 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 118, no 24, 6199-6206 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: There are inconsistent data regarding the association between metabolic factors, separately and combined, and the risk of prostate cancer and death from prostate cancer.

METHODS: In the Metabolic Syndrome and Cancer Project (Me-Can), data on body mass index (BMI); blood pressure; and blood levels of glucose, cholesterol, and triglycerides were collected for 289,866 men. Cox proportional hazard models were used to calculate relative risks (RRs) by exposures in quintiles as well as for z scores (with a mean of 0 and a standard deviation of 1) together with a composite sum of scores to assess the combined effect of metabolic factors. RRs were corrected for random errors in measurement.

RESULTS: During a mean follow-up of 12 years, 6673 men were diagnosed with prostate cancer and 961 died of the disease. Men with high levels of glucose and triglycerides were found to have a decreased risk of prostate cancer: top versus bottom quintile of glucose: RR, 0.82 (95% confidence interval [95% CI], 0.62-1.08; P value for trend = .03) and top versus bottom quintile of triglycerides: RR, 0.88 (95% CI, 0.74-1.04; P value for trend = .001). High BMI, elevated blood pressure, and a high composite z score were found to be associated with an increased risk of death from prostate cancer: top versus bottom quintile of BMI: RR, 1.36 (95% CI, 1.08-1.71); systolic blood pressure: RR, 1.62 (95% CI, 1.07-2.45); and per 1-unit increase of the composite z score: RR, 1.13 (95% CI, 1.03-1.25).

CONCLUSIONS: The authors found no evidence of an association between high levels of metabolic factors and the risk of prostate cancer, but high BMI, elevated blood pressure, and a composite score of all metabolic factors were associated with an increased risk of death from prostate cancer. 

Keyword
epidemiology, metabolic factors, prostate cancer, metabolic syndrome, cohort study, body mass index, blood pressure
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-64958 (URN)10.1002/cncr.27677 (DOI)000311911600025 ()
Available from: 2013-02-26 Created: 2013-02-04 Last updated: 2017-12-06Bibliographically approved
2. Competing risk analysis of metabolic factors and prostate cancer
Open this publication in new window or tab >>Competing risk analysis of metabolic factors and prostate cancer
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Men at risk of prostate cancer are also at risk of competing events but this has been ignored in most studies of metabolic aberrations and prostate cancer. The aim of this study was to assess probabilities of prostate cancer and prostate cancer death by use of competing risk analysis.

Methods: In the Metabolic syndrome and Cancer project (Me-Can), data on body mass index, blood pressure, glucose, total cholesterol, and triglycerides were collected from 285 040 men. Probabilities of prostate cancer, prostate cancer death and competing events, i.e. all-cause death or death from other causes, respectively, were calculated for men with normal (bottom 84%) and high (top 16%) levels of each metabolic factor and a composite score based on all metabolic factors

Results: During follow up, 5893 men were diagnosed with prostate cancer, 1013 men died of prostate cancer, and 26 328 men died of other causes. Men with high levels of metabolic factors had decreased probability of prostate cancer, similar probability of prostate cancer death, and increased probability of other causes of death compared to men with normal levels. After 1996, when prostate specific antigen was used for detection of prostate cancer, men up to 80 years with normal levels of metabolic factors had 13% probability of prostate cancer and 37% probability of death from all causes. For men with high levels of metabolic factors, corresponding probabilities were 12% and 47%.

Conclusions: Men with metabolic aberrations had a decreased probability of prostate cancer but a substantially higher probability of death from all causes.

Keyword
cohort study, competing risk, epidemiology, metabolic factors, prostate cancer
National Category
Cancer and Oncology Urology and Nephrology
Research subject
Epidemiology; Oncology
Identifiers
urn:nbn:se:umu:diva-83945 (URN)
Funder
Swedish Cancer Society, 2010/628
Available from: 2013-12-11 Created: 2013-12-11 Last updated: 2014-01-15Bibliographically approved
3. Metabolic factors associated with risk of renal cell carcinoma
Open this publication in new window or tab >>Metabolic factors associated with risk of renal cell carcinoma
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2, e57475- p.Article in journal (Refereed) Published
Abstract [en]

Previous studies have shown that obesity and hypertension are associated with increased risk of renal cell carcinoma (RCC), but less is known about the association to other metabolic factors. In the Metabolic Syndrome and Cancer project (Me-Can) data on body mass index (BMI, kg/m2), blood pressure, and circulating levels of glucose, cholesterol, and triglycerides were collected from 560,388 men and women in cohorts from Norway, Austria, and Sweden. By use of Cox proportional hazard models, hazard ratios (HR) were calculated for separate and composite metabolic exposures. During a median follow-up of 10 years, 592 men and 263 women were diagnosed with RCC. Among men, we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 1.51, 95% CI 1.13-2.03), systolic blood pressure, (HR = 3.40, 95% CI 1.91-6.06), diastolic blood pressure, (HR = 3.33, 95% CI 1.85-5.99), glucose, (HR = 3.75, 95% CI 1.46-9.68), triglycerides, (HR = 1.79, 95% CI 1.00-3.21) and a composite score of these metabolic factors, (HR = 2.68, 95% CI 1.75-4.11). Among women we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 2.21, 95% CI 1.32-3.70) and the composite score, (HR = 2.29, 95% CI 1.12-4.68). High levels of the composite score were also associated with risk of death from RCC among both men and women. No multiplicative statistical or biological interactions between metabolic factors on risk of RCC were found. High levels of BMI, blood pressure, glucose and triglycerides among men and high BMI among women were associated with increased risk of RCC.

National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-67967 (URN)10.1371/journal.pone.0057475 (DOI)000315524900094 ()
Note

Finansiär: Lion’s Cancer Research Foundation, Umeå University, Sweden (LP 09-1799)

Available from: 2013-04-11 Created: 2013-04-09 Last updated: 2017-12-06Bibliographically approved
4. Metabolic syndrome and risk of bladder cancer: prospective cohort study in the metabolic syndrome and cancer project (Me-Can)
Open this publication in new window or tab >>Metabolic syndrome and risk of bladder cancer: prospective cohort study in the metabolic syndrome and cancer project (Me-Can)
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2011 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, no 8, 1890-1898 p.Article in journal (Refereed) Published
Abstract [en]

There are little data on the putative association between factors in the metabolic syndrome (MetS) and risk of bladder cancer. In the Metabolic Syndrome and Cancer project (Me-Can), measurements of height, weight, blood pressure and circulating levels of glucose, cholesterol, and triglycerides had been collected from 578,700 subjects in cohorts in Norway, Austria, and Sweden. We used Cox proportional hazard models to calculate relative risks (RRs) of bladder cancer by exposures divided into quintiles, in categories according to the World Health Organisation (WHO) and as a continuous standardized variable (z-score with mean = 0 and standard deviation = 1) for each separate component and its standardized sum, a composite MetS score. RRs were corrected for random error in measurements. During a mean follow-up of 11.7 years (SD = 7.6), 1,587 men and 327 women were diagnosed with bladder cancer. Significant associations with risk were found among men per one unit increment of z-score for blood pressure, RR = 1.13 (95% CI 1.03-1.25), and the composite MetS score, RR = 1.10 (95% CI 1.01-1.18). Among women, glucose was nonsignificantly associated with risk, RR = 1.41 (95% CI 0.97-2.06). No statistically significant interactions were found between the components in the MetS in relation to bladder cancer risk. Hypertension and a composite MetS score were significantly but modestly associated with an increased risk of bladder cancer among men and elevated glucose was associated with a nonsignificant increase in risk among women.

Keyword
epidemiology;bladder cancer;metabolic syndrome;cohort study
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-41164 (URN)10.1002/ijc.25521 (DOI)000288037400015 ()20568111 (PubMedID) (ISBN)
Projects
Available from: 2011-03-18 Created: 2011-03-18 Last updated: 2017-12-11Bibliographically approved

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