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Fathering of dizygotic twins and risk of prostate cancer: nationwide, population-based case-control study
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. (Pär Stattin)
Regional Cancer Centre, Uppsala University Hospital, Uppsala, Sweden.
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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2014 (English)In: PLoS ONE, 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.

Place, publisher, year, edition, pages
2014. Vol. 9, no 10, e110506- p.
National Category
Cancer and Oncology
URN: urn:nbn:se:umu:diva-96816DOI: 10.1371/journal.pone.0110506ISI: 000343674800049OAI: diva2:769944

Originally included in thesis in manuscript form.

Available from: 2014-12-09 Created: 2014-12-03 Last updated: 2015-08-31Bibliographically approved
In thesis
1. Prospective studies of hormonal and life-style related factors and risk of cancer
Open this publication in new window or tab >>Prospective studies of hormonal and life-style related factors and risk of cancer
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.
Umeå University medical dissertations, ISSN 0346-6612 ; 1648
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
urn:nbn:se:umu:diva-88308 (URN)978-91-7601-029-7 (ISBN)
Public defence
2014-06-05, Bergasalen, Umeå Universitetssjukhus, byggnad 27, Umeå, 09:00 (Swedish)
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

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