Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3)

Jiyoung Ahn, Fredrick R. Schumacher, Sonja I. Berndt, Ruth Pfeiffer, Demetrius Albanes, Gerald L. Andriole, Eva Ardanaz, Heiner Boeing, Bas Bueno-de-Mesquita, Stephen J. Chanock, Françoise Clavel-Chapelon, W. Ryan Diver, Heather Spencer Feigelson, J. Michael Gaziano, Edward Giovannucci, Christopher A. Haiman, Brian E. Henderson, Robert N. Hoover, Laurence N. Kolonel, Peter KraftJing Ma, Loïc Le Marchand, Kim Overvad, Domenico Palli, Pär Stattin, Meir Stampfer, Daniel O. Stram, Gilles Thomas, Michael J. Thun, Ruth C. Travis, Dimitrios Trichopoulos, Jarmo Virtamo, Stephanie J. Weinstein, Meredith Yeager, Rudolf Kaaks, David J. Hunter, Richard B. Hayes

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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), 3α-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 × 10 -21), consistent with previous studies, and testosterone (P = 7.54 × 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 × 10 -6) and SRD5A2 with 3α-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 × 10 -6). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.

Original languageEnglish
Pages (from-to)3749-3757
Number of pages9
JournalHuman molecular genetics
Volume18
Issue number19
DOIs
StatePublished - Oct 1 2009

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    Ahn, J., Schumacher, F. R., Berndt, S. I., Pfeiffer, R., Albanes, D., Andriole, G. L., Ardanaz, E., Boeing, H., Bueno-de-Mesquita, B., Chanock, S. J., Clavel-Chapelon, F., Diver, W. R., Feigelson, H. S., Gaziano, J. M., Giovannucci, E., Haiman, C. A., Henderson, B. E., Hoover, R. N., Kolonel, L. N., ... Hayes, R. B. (2009). Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3). Human molecular genetics, 18(19), 3749-3757. https://doi.org/10.1093/hmg/ddp302