Journal Article

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<sup>†</sup>

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

in Human Molecular Genetics

Volume 19, issue 19, pages 3873-3884
Published in print October 2010 | ISSN: 0964-6906
Published online July 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq291
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†

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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 (Ptrend = 1.5 × 10−4). 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.

Journal Article.  6808 words.  Illustrated.

Subjects: Genetics and Genomics

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