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Prospective studies of hormonal and life-style related factors and risk of cancer
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Androgens are important in prostate cancer development but how circulating levels of androgens affect risk of prostate cancer of different aggressiveness is not clear. Being childless has been associated with a lower risk of prostate cancer, but it is not clear if this association is causal or a result of residual confounding. Fathering of dizygotic twins, a marker of high fertility, has not been studied in relation to risk of prostate cancer.

Another marker of life-long hormonal exposure is height, which has been associated with increased risk of cancer and cancer death. However, the association to separate cancer sites has not been consistent.

The aims of this thesis were to study hormonal factors (paper I), and proxies of hormonal factors (paper II and III), and risk of prostate cancer; as well as height and risk of cancer and cancer death by separate sites (paper IV).

Methods: Study designs were i) case-control studies, nested within the Västerbotten Intervention Project (paper I), and in Prostate Cancer database Sweden 2.0 (PCBaSe 2.0) (paper II and III), and ii) cohort study, in the Metabolic Syndrome and Cancer project (Me-Can) (paper IV).

Results, prostate cancer: In paper I, increasing levels of serum androgens were not associated with risk of prostate cancer overall or in tumor risk categories. In paper II, childless men had a lower risk of prostate cancer, overall and in all risk categories, compared to fathers, an association which was in part explained by differences in marital status and educational level.  In paper III, fathers of dizygotic twins did not have an increased risk of prostate cancer, either overall or in risk categories, when compared to fathers of singletons.

Results, cancer overall: In paper IV, height was associated with an increased risk of cancer and cancer death overall in both women and men. The strongest association for cancer was to malignant melanoma in both women and men, and for cancer death to post-menopausal breast cancer in women and renal cell carcinoma in men.

Conclusions: These studies indicate that hormonal factors, when studied as serum levels or when studied using proxies of fertility, do not have a major impact on the risk of prostate cancer. The association between height and an increased risk of cancer appears robust for total cancer and cancer death, as well as for several separate cancer sites.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2014. , 76 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1648
Keyword [en]
prostate cancer, epidemiology, androgens, risk factors, fatherhood status, dizygotic twins, height, cohort, case-control, prospective
National Category
Urology and Nephrology Cancer and Oncology
Research subject
Cancer Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-88308ISBN: 978-91-7601-029-7 (print)OAI: oai:DiVA.org:umu-88308DiVA: diva2:715361
Public defence
2014-06-05, Bergasalen, Umeå Universitetssjukhus, byggnad 27, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Funder
Swedish Cancer Society, 11 0471Swedish Research Council, 825-2010-5950
Available from: 2014-05-07 Created: 2014-04-30 Last updated: 2014-12-09Bibliographically approved
List of papers
1. Androgens and prostate cancer risk: a prospective study
Open this publication in new window or tab >>Androgens and prostate cancer risk: a prospective study
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2007 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 67, no 11, 1230-1237 p.Article in journal (Refereed) Published
Abstract [en]

Background: Androgens have been implicated in prostate tumorigenesis, but prospective studies have overall reported no association between circulating levels of androgens and risk of prostate cancer. However, some recent studies have shown that a high level of testosterone increase the risk of non-aggressive tumors but is associated with a decreased risk of aggressive tumors.

Methods: We prospectively measured plasma levels of total testosterone, androstanediol glucuronide (A-diol-g) and sex hormone binding globuline (SHBG) and calculated estimated levels of free testosterone, in a nested case-control study of 392 cases and 392 matched controls.

Results: None of the studied hormones were significantly associated with prostate cancer risk in the full study group or in subgroups according to tumor aggressiveness. Odds ratios in the full study group, for top versus bottom quartile, was for total testosterone 1.25 (95% CI = 0.79–2.00; Ptrend = 0.51); free testosterone, 1.31 (95% CI = 0.82–2.07; Ptrend = 0.35); A-diol-g, 0.88 (95% CI = 0.59–1.33; Ptrend = 0.77); and for SHBG, 1.01 (95% CI = 0.64–1.58; Ptrend = 0.94).

Conclusions: We found no significant associations between androgen levels and risk of prostate cancer in this population-based, non-screened cohort.

Place, publisher, year, edition, pages
John Wiley & Sons, 2007
Keyword
Androgens, epidemiology, prospective studies, prostatic neoplasms
National Category
Public Health, Global Health, Social Medicine and Epidemiology Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-17972 (URN)10.1002/pros.20588 (DOI)000248537500010 ()17562541 (PubMedID) (ISBN)
Projects
Funder
Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2015-04-22Bibliographically approved
2. Fatherhood status and risk of prostate cancer: nationwide, population-based case-control study
Open this publication in new window or tab >>Fatherhood status and risk of prostate cancer: nationwide, population-based case-control study
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2013 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 4, 937-943 p.Article in journal (Refereed) Published
Abstract [en]

Previous studies have shown a decreased risk of prostate cancer for childless men; however, the cause of the association remains to be elucidated. The aim of our study was to assess the risk of prostate cancer by fatherhood status, also considering potential confounding factors. In a case–control study in Prostate Cancer data Base Sweden 2.0, a nationwide, population-based cohort, data on number of children, marital status, education, comorbidity and tumor characteristics obtained through nationwide healthcare registers and demographic databases for 117,328 prostate cancer cases and 562,644 controls, matched on birth year and county of residence, were analyzed. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for prostate cancer overall and by risk category, adjusting for marital status and education. Childless men had a decreased risk of prostate cancer compared to fathers, OR = 0.83 (95% CI = 0.82–0.84), and risk was lower for low-risk prostate cancer, OR = 0.74 (95% CI = 0.72–0.77), than for metastatic prostate cancer, OR = 0.93 (95% CI = 0.90–0.97). Adjustment for marital status and education attenuated the association in the low-risk category, adjusted OR = 0.87 (95% CI = 0.84–0.91), whereas OR for metastatic cancer remained virtually unchanged, adjusted OR = 0.92 (95% CI = 0.88–0.96). Our data indicate that the association between fatherhood status and prostate cancer to a large part is due to socioeconomic factors influencing healthcare-seeking behavior including testing of prostate-specific antigen levels.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
Keyword
prostate cancer, epidemiology, case-control studies, hypogonadism, androgens
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-70196 (URN)10.1002/ijc.28057 (DOI)000320194400017 ()
Funder
Swedish Research Council, 825-2010-5950
Available from: 2013-05-07 Created: 2013-05-07 Last updated: 2017-12-06Bibliographically approved
3. Fathering of dizygotic twins and risk of prostate cancer: nationwide, population-based case-control study
Open this publication in new window or tab >>Fathering of dizygotic twins and risk of prostate cancer: nationwide, population-based case-control study
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 10, e110506- p.Article in journal (Refereed) Published
Abstract [en]

Background: An association between male fertility and risk of prostate cancer has been suggested, possibly through lower androgen levels in subfertile men. We evaluated male fertility in relation to risk of prostate cancer by assessing the frequency of fathering of dizygotic twins, a marker of high fertility, among cases of prostate cancer and controls. Methods: We performed a case-control study in Prostate Cancer data Base Sweden (PCBaSe), a nationwide, population-based cohort. PCBaSe was linked to the Swedish twin register for information on zygosity for same-sex twins and to other nationwide health care registers and demographic databases for information on socioeconomic factors, comorbidity, and tumor characteristics for 96 301 prostate cancer cases and 378 583 matched controls. To account for the influence of in vitro fertilization on dizygotic twinning, analyses were restricted to men who had fathered children before 1991, when in vitro fertilization was still uncommon in Sweden. Results: 1 112 cases and 4 538 controls had fathered dizygotic twins. Men with dizygotic twins had no increased risk of prostate cancer compared to fathers of singletons; neither for total prostate cancer odds ratio (OR) 0.95(95% CI 0.89-1.02), nor for any risk category, OR 0.97 (95% CI 0.84-1.12) for low-risk disease, and OR 1.04 (95% CI 0.90-1.22) for metastatic disease. Conclusion: The lack of association between fathering of dizygotic twins and prostate cancer risk give no support for an association between male fertility and prostate cancer risk.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-96816 (URN)10.1371/journal.pone.0110506 (DOI)000343674800049 ()
Note

Originally included in thesis in manuscript form.

Available from: 2014-12-09 Created: 2014-12-03 Last updated: 2017-12-05Bibliographically approved
4. Pooled cohort study on height and risk of cancer and cancer death
Open this publication in new window or tab >>Pooled cohort study on height and risk of cancer and cancer death
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2014 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, no 2, 151-159 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To assess the association between height and risk of cancer and cancer death.

METHODS: The metabolic syndrome and cancer project is a prospective pooled cohort study of 585,928 participants from seven cohorts in Austria, Norway, and Sweden. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model.

RESULTS: During a mean follow-up of 12.7 years (SD = 7.2), 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer. Increased height (per 5-cm increment) was associated with an increased overall cancer risk in women, HR 1.07 (95 % CI 1.06-1.09), and in men, HR 1.04 (95 % CI 1.03-1.06). The highest HR was seen for malignant melanoma in women, HR 1.17 (95 % CI 1.11-1.24), and in men HR 1.12 (95 % CI 1.08-1.19). Height was also associated with increased risk of cancer death in women, HR 1.03 (95 % CI 1.01-1.16), and in men, HR 1.03 (95 % CI 1.01-1.05). The highest HR was observed for breast cancer death in postmenopausal women (>60 years), HR 1.10 (95 % CI 1.00-1.21), and death from renal cell carcinoma in men, HR 1.18 (95 % CI 1.07-1.30). All these associations were independent of body mass index.

CONCLUSION: Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2014
Keyword
Body stature, Body height, Epidemiology, Cancer risk, Cohort study
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:umu:diva-82646 (URN)10.1007/s10552-013-0317-7 (DOI)000330848600002 ()24173535 (PubMedID)
Available from: 2013-11-06 Created: 2013-11-06 Last updated: 2017-12-06Bibliographically approved

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