Polyunsaturated fatty acids, genetic susceptibility, and breast cancer incidence and survival

Khankari, Nikhil

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March 19, 2019

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Khankari, Nikhil
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology

Abstract

Laboratory studies have demonstrated that ω-3 polyunsaturated fatty acids (PUFAs) inhibit inflammatory eicosanoids generated by ω-6 PUFAs metabolism. Additionally, ω-3 PUFAs have been shown to induce a cytotoxic environment thereby increasing apoptosis and reducing cell growth in breast cancer cells. Despite this biologic plausibility, epidemiologic investigations of dietary PUFA intake and breast cancer are inconclusive among Western populations. This ancillary study examined the impact of dietary PUFA and fish (a primary source of beneficial long-chain (LC) ω-3 PUFAs) intake, and genetic susceptibility in biologically relevant pathways (i.e., inflammation, oxidative stress, and estrogen metabolism) on: the risk of breast cancer (Aim 1); and survival following a first, primary breast cancer diagnosis (Aim 2). To address these aims, resources from the Long Island Breast Cancer Study Project (LIBCSP), a case-control study of 1463 breast cancer cases and 1500 controls were utilized. Additionally, vital status for the population-based cases was determined through 2011, yielding a median follow-up time of 14.7 years and 485 deaths. Adjusted odds ratios (ORs) and hazard ratios (HRs), and corresponding 95% confidence intervals (CIs), were estimated using unconditional logistic regression and Cox-proportional hazards regression, respectively. We observed a super-additive interaction (Relative Excess Risk Due to Interaction=0.43; 95% CI=0.09, 0.78) between ω-3 and ω-6 intake in association with breast cancer risk, though the CIs for the joint exposure of low ω-3 and high ω-6 compared to high ω-3 and low ω-6 intake were imprecise (OR=1.21; 95% CI=0.86, 1.70). No interactions were observed with polymorphisms considered, but odds were elevated for low ω-3/ω-6 ratio across genotypes. All-cause mortality was reduced by 25-29% among women with breast cancer reporting the highest quartile of intake (compared to never) for: tuna (HR=0.71, 95% CI=0.55, 0.92); other baked/broiled fish (HR=0.75, 95% CI=0.58, 0.97); and dietary long-chain ω-3 PUFAs docosahexanoic (DHA, HR=0.71, 95% CI=0.55, 0.92) and eicosapentanoic (EPA, HR=0.75, 95% CI=0.58, 0.97) acid. Breast cancer risk reduction may be possible for U.S. women with dietary consumption of both higher ω-3 and lower ω-6. Additionally, LC ω-3 PUFA intake from fish and other dietary sources may provide a potential strategy to improve survival after breast cancer.

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