Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium

Author： Canzian Federico Cox David G. Setiawan V. Wendy Stram Daniel O. Ziegler Regina G. Dossus Laure Beckmann Lars Blanch Hlne Barricarte Aurelio Berg Christine D. Bingham Sheila Buring Julie Buys Saundra S. Calle Eugenia E. Chanock Stephen J. Clavel-Chapelon Franoise DeLancey John Oliver L. Diver W. Ryan Dorronsoro Miren Haiman Christopher A. Hallmans Gran Hankinson Susan E. Hunter David J. Hsing Anika Isaacs Claudine Khaw Kay-Tee Kolonel Laurence N. Kraft Peter Le Marchand Loc Lund Eiliv Overvad Kim Panico Salvatore Peeters Petra H.M. Pollak Michael Thun Michael J. Tjnneland Anne Trichopoulos Dimitrios Tumino Rosario Yeager Meredith Hoover Robert N. Riboli Elio Thomas Gilles Henderson Brian E. Kaaks Rudolf Feigelson Heather Spencer

Publisher： Oxford University Press

ISSN： 1460-2083

Source： Human Molecular Genetics, Vol.19, Iss.19, 2010-10, pp. : 3873-3884

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Abstract

There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3 of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P_trend 1.5 10⁴). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk.