Journal of the National Cancer Institute Advance Access originally published online on January 29, 2008
JNCI Journal of the National Cancer Institute 2008 100(3):170-183; doi:10.1093/jnci/djm323
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© The Author 2008. Published by Oxford University Press.
ARTICLES |
Endogenous Sex Hormones and Prostate Cancer: A Collaborative Analysis of 18 Prospective Studies
Correspondence to: Andrew W. Roddam, D.Phil, Cancer Research UK Epidemiology Unit, University of Oxford, Richard Doll Building, Oxford, UK, OX3 7LF (e-mail: andrew.roddam{at}ceu.ox.ac.uk).
Background: Sex hormones in serum have been hypothesized to influence the risk of prostate cancer. We performed a collaborative analysis of the existing worldwide epidemiologic data to examine these associations in a uniform manner and to provide more precise estimates of risks.
Methods: Data on serum concentrations of sex hormones from 18 prospective studies that included 3886 men with incident prostate cancer and 6438 control subjects were pooled by the Endogenous Hormones and Prostate Cancer Collaborative Group. Relative risks (RRs) of prostate cancer by fifths of serum hormone concentration were estimated by use of conditional logistic regression with stratification by study, age at recruitment, and year of recruitment. All statistical tests were two-sided.
Results: No associations were found between the risk of prostate cancer and serum concentrations of testosterone, calculated free testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, androstanediol glucuronide, estradiol, or calculated free estradiol. The serum concentration of sex hormone–binding globulin was modestly inversely associated with prostate cancer risk (RR in the highest vs lowest fifth = 0.86, 95% confidence interval = 0.75 to 0.98; Ptrend = .01). There was no statistical evidence of heterogeneity among studies, and adjustment for potential confounders made little difference to the risk estimates.
Conclusions: In this collaborative analysis of the worldwide data on endogenous hormones and prostate cancer risk, serum concentrations of sex hormones were not associated with the risk of prostate cancer.
| CONTEXT AND CAVEATS Prior knowledge Sex hormones in serum could, hypothetically, influence the risk of prostate cancer. Study design Pooled analysis of 18 prospective studies on the association between sex hormone concentrations in serum and the risk of prostate cancer. A total of 3886 men with incident prostate cancer and 6438 control subjects were included in this analysis. Contribution No associations were found between the risk of prostate cancer and serum concentrations of testosterone, calculated free testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, androstanediol glucuronide, estradiol, or calculated free estradiol. A modest inverse association was observed between the risk of prostate cancer and the serum concentration of sex hormone–binding globulin. Implications Sex hormones apparently do not influence the risk of prostate cancer. Limitations Possible biases could have been introduced because of the long latency associated with prostate cancer, which could result in some control subjects having occult disease. Different laboratory methods were used in different studies to measure sex hormone concentrations in serum. Hormone concentrations were measured in only one sample for each participant.
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Endogenous Hormones and Prostate Cancer Collaborative Group.
Authors/writing committee: Andrew W. Roddam, Naomi E. Allen, Paul Appleby, and Timothy J. Key (Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK).
Authors/members of the collaboration:
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: Joanne F. Dorgan (Fox Chase Cancer Center, Philadelphia, PA), Demetrius Albanes and Philip R. Taylor (Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MA). (The ATBC study would like to acknowledge the support of J. Virtamo, O. Heinonen (who is deceased now), D. W. Chandler, M. Galmarini, L. M. McShane, M. J. Barrett, and J. Tangrea.)
Baltimore Longitudinal Study of Aging: Luigi Ferrucci, Director (Clinical Research Branch, National Institute on Aging, Baltimore, MD); H. Ballentine Carter (The James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutes, Baltimore, MD); E. Jeffrey Metter (Clinical Research Branch, National Institute on Aging, Baltimore, MD). (The Baltimore Longitudinal Study of Aging is supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging).
Carotene and Retinol Efficacy Trial (CARET): Chu Chen, Noel S Weiss (University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA); Gary Goodman (Fred Hutchinson Cancer Research Center and Swedish Cancer Institute, Seattle, WA). (CARET would like to acknowledge the support of F. Z. Stanczyk, S. K. Lewis, R. Etzioni, M. Barnett, D. DiTommaso, and the CARET study participants.)
CLUE Study, Washington County, MD: Ann W. Hsing (Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD); George Comstock (who is deceased now; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD); Kathy Helzlsouer (Prevention and Research Center, The Weinberg Center for Women's Health and Medicine, Mercy Medical Center, Baltimore, MD and Johns Hopkins Bloomberg School of Public Health, Baltimore, MD).
European Prospective Investigation into Cancer and Nutrition: Ruth Travis (Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK); Elio Riboli (Department of Epidemiology and Public Health, Imperial College, London, UK); Rudolf Kaaks (Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany).
Finnish Mobile Clinic Health Examination Survey: Paul Knekt, Markku Heliövaara (National Public Health Institute, Helsinki, Finland).
Health Professionals Follow-up Study (HPFS): Elizabeth A. Platz (Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, the Brady Urological Institute and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD); Walter C. Willett, Edward Giovannucci (Departments of Nutrition and Epidemiology, Harvard School of Public Health and the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA). (The HPFS investigators would like to acknowledge Dr Nader Rifai, whose laboratory performed the hormone assays.)
Janus Serum Bank: Lars Vatten (Department of Community Medicine and General Practice, University of Trondheim, Trondheim, Norway); Giske Ursin (Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, and Department of Nutrition, University of Oslo, Norway). (The Janus Serum Bank Study would like to acknowledge the help of the late R. Ross, F. Stanczyk, R. Lobo, S. Harvei, and E. Jellum.)
Japan Collaborative Cohort Study: Akiko Tamakoshi (National Center for Geriatrics and Gerontology, Obu, Japan); Kotaro Ozasa (Kyoto Prefectural University of Medicine, Kyoto, Japan).
Japan-Hawaii Cancer Study (JHCS): Abraham M. Y. Nomura (Japan-Hawaii Cancer Study, Kuakini Medical Center, Honolulu, HI); Grant N. Stemmermann (Department of Pathology, University of Cincinnati Medical Center, Cincinnati, OH). (JHCS would like to acknowledge the support of F. Z. Stanczyk and H. L. Judd.)
Kaiser Permanente Medical Care Program: Catherine Schaefer, Charles P. Quesenberry Jr (Division of Research, Kaiser Permanente Northern California, Oakland, CA); Joseph H. Vogelman (Orentreich Foundation for the Advancement of Science, Inc., New York).
Melbourne Collaborative Cohort Study: Gianluca Severi, Dallas R. English, Graham G. Giles (Cancer Epidemiology Centre, The Cancer Council Victoria and Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia).
Nordic Biological Specimen Biobank Working Group—Finland: Tapio Luostarinen (Finnish Cancer Registry, Helsinki, Finland); Ulf-Håkan Stenman (Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland); Leena Tenkanen (Helsinki Heart Study, Helsinki, Finland, and University of Tampere, Tampere, Finland).
Nordic Biological Specimen Biobank Working Group—Norway: Randi Gislefoss (The Norwegian Cancer Registry, Oslo, Norway). (The Janus Serum Bank, owned by The Norwegian Cancer Society, provided serum samples.)
Northern Sweden Health and Disease Cohort: Pär Stattin (Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden); Göran Hallmans (Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University Hospital, Umeå, Sweden); Tanja Stocks (Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden).
Physicians’ Health Study: June M. Chan (Departments of Epidemiology and Biostatistics and Urology, University of California, San Francisco, CA); Meir Stampfer (Departments of Nutrition and Epidemiology, Harvard School of Public Health and the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA); Peter Gann (Department of Pathology, University of Illinois at Chicago, Chicago, IL).
Prostate Testing for Cancer and Treatment: Steven E. Oliver (Department of Health Sciences, University of York and the Hull York Medical School, York, UK); Jeff M. Holly (Division of Surgery, Bristol Royal Infirmary, Bristol, UK); Jenny Donovan (Department of Social Medicine, University of Bristol, Bristol, UK). (ProtecT would like to acknowledge the support of D. Gunnell, T. J. Peters, R. Persad, D. Gillatt, A. Pearce, D. E. Neal, F. C. Hamdy, and the ProtecT research team.)
Rancho Bernardo Study: Elizabeth Barrett-Connor, Cedric Garland (University of California, San Diego, CA).
The central pooling and analysis of these data were supported by Cancer Research UK. Cancer Research UK had no role in the design, conduct, data management and analysis; in the manuscript preparation or review; or in the authorization for submission.
Manuscript received June 5, 2007; revised December 6, 2007; accepted December 19, 2007.
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