Genetic Polymorphisms of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor Binding Protein 3, Xenoestrogen, Phytoestrogen, and Premenopausal Breast Cancer

Background: Previous studies suggest a combined effect of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) gene polymorphisms, xenoestrogen, and phytoestrogen on the IGF-1 signalling pathway and serum concentrations in the IGF system, which are associated with premenopausal breast cancer (BCa) risk. Methods: Between 2010 and 2012, our study recruited 140 premenopausal BCa patients and 160 community-based premenopausal control subjects. Participants were surveyed about oral contraceptive (OC) use, dietary habits, and other BCa risk factors. TaqMan assays were used to determine IGF-1 rs1520220 and IGFBP-3 rs2854744 genotypes. Daily intakes of energy-adjusted soy isoflavones (EASIs) were calculated by the residual method. Multivariate logistic regression was applied to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the IGF-1 rs1520220 and IGFBP-3 rs2854744 genotypes, OC use, and intake of EASIs. Stratified analyses were performed to detect the gene–environment combined effect, and multivariate logistic regression was used to estimate interaction coefficients (IORs) by the multiplicative model, with 95% CIs. The delta method was used to calculate interaction coefficients by the additive model [relative excess risk of interaction (RERI), attributable proportions of interaction (APIs)] and 95% CIs. Results: The IGF-1 and IGFBP-3 genotypes, OC use, and EASIs were not found to be associated with BCa risk (p > 0.05). Stratified analysis showed that the risk of BCa was markedly increased in women carrying the IGFBP-3C allele and using OCs compared with women either carrying the IGFBP-3C allele or using ocs (OR: 3.02; 95% CI: 1.04 to 8.79). The interaction coefficients IOR, RERI, and API were 4.89 (95% CI: 1.09 to 21.90), 2.42 (95% CI: −0.76 to 5.61), and 0.80 (95% CI: 0.46 to 1.67) respectively. Conclusions: The IGFBP-3 rs2854744 polymorphism and OC use might synergistically increase premenopausal BCa risk.