IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3)

• Published in: PloS one 2008-07, Vol.3 (7), p.e2578-e2578
• Main Authors: Patel, Alpa V, Cheng, Iona, Canzian, Federico, Le Marchand, Loïc, Thun, Michael J, Berg, Christine D, Buring, Julie, Calle, Eugenia E, Chanock, Stephen, Clavel-Chapelon, Francoise, Cox, David G, Dorronsoro, Miren, Dossus, Laure, Haiman, Christopher A, Hankinson, Susan E, Henderson, Brian E, Hoover, Robert, Hunter, David J, Kaaks, Rudolf, Kolonel, Laurence N, Kraft, Peter, Linseisen, Jakob, Lund, Eiliv, Manjer, Jonas, McCarty, Catherine, Peeters, Petra H M, Pike, Malcolm C, Pollak, Michael, Riboli, Elio, Stram, Daniel O, Tjonneland, Anne, Travis, Ruth C, Trichopoulos, Dimitrios, Tumino, Rosario, Yeager, Meredith, Ziegler, Regina G, Feigelson, Heather Spencer
• Format: Article
• Language: English
• Subjects: Animal models; Binding proteins; Bioavailability; Biomarkers; Body mass; Body mass index; Breast cancer; Breast Neoplasms - genetics; Cancer; Carcinogenesis; Carcinogens; Cell proliferation; Chromosomes; Cohort Studies; Consortia; Epidemiology; Female; Genes; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetics; Genotype; Haplotypes; Health aspects; Health care; Health risk assessment; Health risks; Health surveillance; Hospitals; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1 - blood; Insulin-Like Growth Factor Binding Protein 1 - genetics; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factor-binding protein 1; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; Linkage Disequilibrium; Male; Medical research; Plasma; Polymorphism, Genetic; Post-menopause; Postmenopausal women; Preventive medicine; Prostate cancer; Prostatic Neoplasms - genetics; Protein binding; Proteins; Public health; Public Health and Epidemiology/Epidemiology; Regression analysis; Risk; Risk Factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Tagging; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0002578

IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.