TY - JOUR
T1 - CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium
AU - Travis, Ruth C.
AU - Schumacher, Fredrick
AU - Hirschhorn, Joel N.
AU - Kraft, Peter
AU - Allen, Naomi E.
AU - Albanes, Demetrius
AU - Berglund, Göran
AU - Berndt, Sonja I.
AU - Boeing, Heiner
AU - Bueno-de-Mesquita, H. Bas
AU - Calle, Eugenia E.
AU - Chanock, Stephen
AU - Dunning, Alison M.
AU - Hayes, Richard
AU - Feigelson, Heather Spencer
AU - Gaziano, J. Michael
AU - Giovannucci, Edward
AU - Haiman, Christopher A.
AU - Henderson, Brian E.
AU - Kaaks, Rudolf
AU - Kolonel, Laurence N.
AU - Ma, Jing
AU - Rodriguez, Laudina
AU - Riboli, Elio
AU - Stampfer, Meir
AU - Stram, Daniel O.
AU - Thun, Michael J.
AU - Tjonneland, Anne
AU - Trichopoulos, Dimitrios
AU - Vineis, Paolo
AU - Virtamo, Jarmo
AU - Le Marchand, Loic
AU - Hunter, David J.
PY - 2009
Y1 - 2009
N2 - Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nuclecitide polymorphisms (htSNP) that efficiently predict common variants in U.S. and Europe-an whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs; in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 x 10(-5)], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2734-44)
AB - Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nuclecitide polymorphisms (htSNP) that efficiently predict common variants in U.S. and Europe-an whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs; in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 x 10(-5)], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2734-44)
U2 - 10.1158/1055-9965.EPI-09-0496
DO - 10.1158/1055-9965.EPI-09-0496
M3 - Article
C2 - 19789370
SN - 1538-7755
VL - 18
SP - 2734
EP - 2744
JO - Cancer Epidemiology Biomarkers & Prevention
JF - Cancer Epidemiology Biomarkers & Prevention
IS - 10
ER -
