Multiple exposure to environmental factors and variations in CYP27B1 and the microRNA‐binding site of IL‐13 are associated with breast cancer risk

PURPOSE: Several molecular epidemiology studies have evidenced an association of environmental factors and genetic polymorphisms with breast cancer (BC) risk. However, most have considered the functions of a single element rather than combined effects. METHODS: This case-control study of 693 newly-diagnosed BC cases and 714 cancer-free controls evaluated the effect of multiple exposures to environmental factors and polymorphisms in CYP27B1 and IL-13 on BC risk. Genotypes were detected using TaqMan genotyping. Combinations and interactions were analyzed using cross-over analysis and multivariate logistic regression. Combining exposure models were assessed using classification and regression tree and multivariate logistic regression analyses. RESULTS: No significant independent association was observed for any polymorphism in CYP27B1 or IL-13 with the risk of BC. However, significant combined effects were noted for ≥1 time/wk physical activity with rs10877012 (adjusted odds ratio [ORadj ] = 0.21, 95% confidence interval [CI] = 0.11-0.39) and rs4646536 (ORadj  = 0.21, 95% CI = 0.11-0.39) in CYP27B1. Furthermore, taking garlic ≥4 times/wk, ≥1 time/wk physical activity, and a psychological index score ≥33 all displayed significant combined effects with three IL-13 polymorphisms. These relationships remained significant after Bonferroni correction for multiple comparisons. Combining exposure models indicated that compared with consuming garlic ≥4 times/wk, five models (model 5, ORadj  = 2.94, 95% CI = 1.07-8.06; model 6, ORadj  = 10.26, 95% CI = 5.81-18.10; model 7, ORadj  = 5.05, 95% CI = 2.78-9.17; model 8, ORadj  = 3.95, 95% CI = 2.79-5.58; and model 9, ORadj  = 7.97, 95% CI = 5.26-12.07) showed a significant increased risk. CONCLUSIONS: Our findings suggest that personalized adjustments to diet and behavioral patterns may aid BC prevention in variant carriers of CYP27B1 and IL-13.