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.
