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. Most molecular epidemiology studies on the association of environmental elements and polymorphisms with breast cancer (BC) risk mainly focused on the functions of single factor in BC while ignoring their combined effects. Our case‐control study indicated significant combined effects for environmental factors with polymorphisms in CYP27B1 (rs10877012, rs4646536) and IL‐13 (rs847, rs848, rs1295685). The results of the classification and regression tree showed significant increased risks of five models in BC.