Data from Body Mass Index, IGF1-Related Polymorphisms, and Risk of Familial Breast Cancer in Women with No BRCA1 or BRCA2 Pathogenic Variant

AbstractBackground: Body mass index (BMI) and some SNPs associated with insulin-like growth factor 1 (IGF1) metabolism are risk factors for breast cancer in the general population. No investigation has been performed in women presenting a familial predisposition to breast cancer, except in women carrying a pathogenic variant in BRCA1 or BRCA2 (BRCA1/2). We investigated the effect of BMI and IGF1-related SNPs in high-risk women with no BRCA1/2 pathogenic variant. Methods: We conducted a case–control study in the GENESIS study (1,556 cases and 1,546 controls). We assessed the association of 639,424 SNPs associated with circulating IGF1 levels or located in genes of Kyoto Encyclopedia of Genes and Genomes pathways involving IGF1 with breast cancer using logistic regression models. Results: A reduced risk of estrogen receptor–positive tumors was observed for premenopausal women with a BMI above 25 kg/m² (OR = 0.52; 95% confidence interval, 0.34–0.81). None of the SNPs were associated with breast cancer except rs117292219 in STAT5A, and an association with a reduced risk of estrogen receptor–negative tumors (OR = 0.41; 95% confidence interval, 0.26–0.66) was observed. No interaction between BMI and any of the analyzed SNPs was observed. Conclusions: Our findings on BMI effect were consistent with those reported in the general population and in BRCA1/2 pathogenic variant carriers: Overweight women have a reduced risk of breast cancer before menopause but no increased risk after menopause. We found few associations between IGF1-related SNPs and familial breast cancer, even if variants at the STAT5A locus warrant further investigation. Impact: This large case–control study does not support a major role of the genetic variability of IGF1 metabolism in familial breast cancer risk in women with no BRCA1/2 pathogenic variant.