Interaction between polyunsaturated fatty acids and genetic variants in relation to breast cancer incidence

Higher intake of ω-3 relative to ω-6 polyunsaturated fatty acids (PUFAs) may reduce breast carcinogenesis via different metabolic pathways. The PUFA-breast cancer association remains inconclusive, thus, we hypothesized that interactions between the ratio of dietary ω-3:ω-6 intake and polymorphisms from PUFA-related metabolic pathways would help elucidate an association. Utilizing resources from the Long Island Breast Cancer Study Project, a population-based case-control study (n=1035 cases/1075 controls), we examined interactions between ω-3:ω-6 ratio and 18 polymorphisms of 15 genes. Compared to the putative lowest risk group (high ω-3:ω-6,low-risk FASL rs763110 CT/TT genotype), the odds ratio (OR) for breast cancer from unconditional logistic regression models was weakly increased for other exposure-genotype combinations (high ω-3:ω-6,high-risk FASL CC genotype, OR=1.18,95% confidence interval(CI)=0.90,1.53; low ω-3:ω-6,CT/TT genotype, OR=1.35,95%CI=1.09,1.66); but was approximately null for the putative highest risk group (low ω-3:ω-6,CC genotype; OR=1.06,95%CI=0.81,1.38). We observed an interaction between the ω-3:ω-6 ratio and FASL rs763110 on the additive scale [Relative Excess Risk Due to Interaction(RERI)=-0.47, 95%CI=-0.92,-0.02]. Interactions with other polymorphisms considered were not evident. Our findings suggest that the PUFA-breast cancer association may be modified by FASL. However, additional research is needed given this interaction may be due to chance and is inconsistent with our a priori biologic hypothesis.