Human Molecular Genetics Advance Access published online on July 2, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp302
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Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3)
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA 2 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA 3 Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA 4 Public Health Institute of Navarra, Pamplona, Spain and CIBER Epidemiología y Salud Pública (CIBERESP), Spain 5 Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany 6 National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands 7 Institut National de la Santé et de la Recherche Médicale(Inserm), ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, F-94805, France 8 Department of Epidemiology and Surveillance Research, American Cancer Society, Williams Street, NW, Atlanta, Georgia 30303-1002, USA 9 Departments of Nutrition and Epidemiology, Harvard School of Public Health, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA 10 Cancer Research Center, University of Hawaii, Honolulu, Hawaii 11 Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA 12 Department of Clinical Epidemiology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark 13 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy 14 Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden 15 Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom 16 Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland, FIN-00300 Finland 17 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany 18 Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, New York, NY, 10016
* Correspondence to: Richard B. Hayes, DDS, PhD, Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, 650 First Ave, New York, NY, 10016, 212-263-9242 (phone); 212-263-8570 (fax); Richard.B.Hayes{at}NYUMC.org (email)
Received March 10, 2009; Revised June 24, 2009; Accepted June 29, 2009
Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N=4,720), testosterone (N=4,678), 3
-androstanediol-glucuronide (N=4,767), and 17β-estradiol (N=2,014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (p=4.52x10–21), consistent with previous studies, and testosterone (p=7.54x10–15), with mean difference of 26.9% and 14.3% respectively, comparing wildtype to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference=8.8%, p=7.37x10–6) and SRD5A2 with 3-androstanediol-glucuronide (rs2208532, mean difference=11.8%, p=1.82x10–6). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.