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CYP17 genetic variation and risk of breast and prostate cancer from the national Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

Setiawan, Veronica Wendy; Schumacher, Fredrick R.; Haiman, Christopher A.; Stram, Daniel O.; Albanes, Demetrius; Altshuler, David; Berglund, Göran LU ; Buring, Julie; Calle, Eugenia E. and Clavel-Chapelon, Francoise, et al. (2007) In Cancer Epidemiology Biomarkers & Prevention 16(11). p.2237-2246
Abstract
CYP17 encodes cytochrome p450c17 alpha, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (R-h(2) >= 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate... (More)
CYP17 encodes cytochrome p450c17 alpha, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (R-h(2) >= 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate cancer cases and 9,033 controls, and 5,333 breast cancer cases and 7,069 controls from the Breast and Prostate Cancer Cohort Consortium. We observed borderline significant associations with prostate cancer for rs2486758 [TC versus TT, odds ratios (OR), 1.07; 95% confidence intervals (95% Cl), 1.00-1.14; CC versus TT, OR, 1.09; 95% CI, 0.95-1.26; P trend = 0.04] and rs6892 (AG versus AA, OR, 1.08; 95% CI, 1.00-1.15; GG versus AA, OR, 1.11; 95% CI, 0.95-1.30; P trend = 0.03). We also observed marginally significant associations with breast cancer for rs4919687 (GA versus GG, OR, 1.04; 95% CI, 0.97-1.12, AA versus GG, OR, 1.17; 95% CI, 1.03-1.34; P trend = 0.03) and rs4919682 (CT versus CC, OR, 1.04; 95% CI, 0.97-1.12; TT versus CC, OR, 1.16; 95% CI, 1.01-1.33; P trend = 0.04). Common variation at CYP17 was not associated with circulating sex steroid hormones in men or postmenopausal women. Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
16
issue
11
pages
2237 - 2246
publisher
American Association for Cancer Research
external identifiers
  • wos:000251123500013
  • scopus:38849095120
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-07-0589
language
English
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yes
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2a3acf1e-89a2-47bc-81b4-6c856191e9de (old id 969213)
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2008-01-30 14:25:58
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2017-05-21 04:26:33
@article{2a3acf1e-89a2-47bc-81b4-6c856191e9de,
  abstract     = {CYP17 encodes cytochrome p450c17 alpha, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (R-h(2) >= 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate cancer cases and 9,033 controls, and 5,333 breast cancer cases and 7,069 controls from the Breast and Prostate Cancer Cohort Consortium. We observed borderline significant associations with prostate cancer for rs2486758 [TC versus TT, odds ratios (OR), 1.07; 95% confidence intervals (95% Cl), 1.00-1.14; CC versus TT, OR, 1.09; 95% CI, 0.95-1.26; P trend = 0.04] and rs6892 (AG versus AA, OR, 1.08; 95% CI, 1.00-1.15; GG versus AA, OR, 1.11; 95% CI, 0.95-1.30; P trend = 0.03). We also observed marginally significant associations with breast cancer for rs4919687 (GA versus GG, OR, 1.04; 95% CI, 0.97-1.12, AA versus GG, OR, 1.17; 95% CI, 1.03-1.34; P trend = 0.03) and rs4919682 (CT versus CC, OR, 1.04; 95% CI, 0.97-1.12; TT versus CC, OR, 1.16; 95% CI, 1.01-1.33; P trend = 0.04). Common variation at CYP17 was not associated with circulating sex steroid hormones in men or postmenopausal women. Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility.},
  author       = {Setiawan, Veronica Wendy and Schumacher, Fredrick R. and Haiman, Christopher A. and Stram, Daniel O. and Albanes, Demetrius and Altshuler, David and Berglund, Göran and Buring, Julie and Calle, Eugenia E. and Clavel-Chapelon, Francoise and Cox, David G. and Gaziano, J. Michael and Hankinson, Susan E. and Hayes, Richard B. and Henderson, Brian E. and Hirschhorn, Joel and Hoover, Robert and Hunter, David J. and Kaaks, Rudolf and Kolonel, Laurence N. and Kraft, Peter and Ma, Jing and Le Marchand, Loic and Linseisen, Jakob and Lund, Eiliv and Navarro, Carmen and Overvad, Kim and Palli, Domenico and Peeters, Petra H. M. and Pike, Malcolm C. and Riboli, Elio and Stampfer, Meir J. and Thun, Michael J. and Travis, Ruth and Trichopoulos, Dimitrios and Yeager, Meredith and Ziegler, Regina G. and Feigelson, Heather Spencer and Chanock, Stephen J.},
  issn         = {1538-7755},
  language     = {eng},
  number       = {11},
  pages        = {2237--2246},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {CYP17 genetic variation and risk of breast and prostate cancer from the national Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-07-0589},
  volume       = {16},
  year         = {2007},
}