Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3).
Ahn J., Schumacher FR., Berndt SI., Pfeiffer R., Albanes D., Andriole GL., Ardanaz E., Boeing H., Bueno-de-Mesquita B., Chanock SJ., Clavel-Chapelon F., Diver WR., Feigelson HS., Gaziano JM., Giovannucci E., Haiman CA., Henderson BE., Hoover RN., Kolonel LN., Kraft P., Ma J., Le Marchand L., Overvad K., Palli D., Stattin P., Stampfer M., Stram DO., Thomas G., Thun MJ., Travis RC., Trichopoulos D., Virtamo J., Weinstein SJ., Yeager M., Kaaks R., Hunter DJ., Hayes RB.
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 alpha-androstanediol-glucuronide (N = 4767) and 17beta-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 alpha-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.