がんの疫学と予防ジャーナル オープンアクセス

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Interaction between Polyunsaturated Fatty Acids and Genetic Variants in Relation to Breast Cancer Incidence

Khankari NK, Bradshaw PT, Steck SE, He KA, Olshan AF, Ahn J, Terry MB, Crew KD, Teitelbaum SL, Neugut NI, Santella RM and Gammon MD

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.