Human Molecular Genetics Advance Access originally published online on July 2, 2009
Human Molecular Genetics 2009 18(19):3749-3757; doi:10.1093/hmg/ddp302
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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, MD, USA, 2 Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, 650 First Ave, New York, NY 10016, USA, 3 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, 4 Division of Urologic Surgery, Washington University School of Medicine, St. Louis, MO, USA, 5 Public Health Institute of Navarra, Pamplona, Spain, 6 CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, 7 Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany, 8 National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, 9 Institut National de la Santé et de la Recherche Médicale (Inserm), ERI 20, Paris EA 4045, France, 10 Institut Gustave Roussy, Villejuif F-94805, France, 11 Department of Epidemiology and Surveillance Research, American Cancer Society, Williams Street, NW, Atlanta, GA 30303-1002, USA, 12 Departments of Nutrition and Epidemiology, and 13 Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, 14 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, 15 Cancer Research Center, University of Hawaii, Honolulu, Hawaii, 16 Department of Clinical Epidemiology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, 17 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy, 18 Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden, 19 Cancer Epidemiology Unit, University of Oxford, Oxford, UK, 20 Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki FIN-00300, Finland and 21 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
* To whom correspondence should be addressed. Tel: +1 2122639242; Fax: +1 2122638570; Email: richard.b.hayes{at}nyumc.org
Received March 10, 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 = 4720), testosterone (N = 4678), 3
-androstanediol-glucuronide (N = 4767) and 17β-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10–21), consistent with previous studies, and testosterone (P = 7.54 x 10–15), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10–6) and SRD5A2 with 3-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10–6). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.