Red Blood Cell Polyunsaturated Fatty Acid Composition and Mortality Following Breast Cancer: Results From the Women's Healthy Eating and Living (WHEL) Study

Abstract

Purpose: To examine the associations between red blood cell (RBC) composition of polyunsaturated fatty acids (PUFAs) and mortality among women with breast cancer. Methods: This nested case-control study included 1,104 women from the Women's Healthy Eating and Living Study, a randomized controlled trial of a plant-based dietary change on breast cancer survival. Cases were women who died from any cause (n = 290) from 1995 to 2006. Controls were women who were alive at the end of follow-up matched to cases on age at diagnosis, years since randomization, intervention group, and stage (n = 814). RBC fatty acid composition was measured in blood samples collected at baseline using gas chromatography and included the proportions of four n-3 and seven n-6 PUFAS. We examined each PUFA individually as well as factor analysis-derived factors in association with all-cause and breast cancer-specific mortality using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: In fully-adjusted models, all-cause mortality ORs were elevated among women with PUFAs >median (versus ≤ median) for alpha-linolenic acid (ALA, C18:3n3; OR = 1.56; 95% CI = 1.14–2.14) and for linolenic acid (LnA, C18:2n6, OR = 1.54; 95% CI = 1.15–2.07), and breast cancer-specific mortality ORs were elevated for LnA (OR = 1.72, 95% CI = 1.24–2.38) and gamma-linolenic acid (GLA, C18:3n6; OR = 1.40; 95% CI = 0.97–2.00). Factor 1 [arachidonic acid, C20:4n6; adrenic acid, C22:4n6; and docosapentaenoic acid, C22:5n6] scores >median (versus ≤median) were associated with lower odds of all-cause (OR = 0.72; 95% CI = 0.53–0.98) and breast cancer-specific (OR = 0.67; 95% CI = 0.47–0.94) mortality, and Factor 4 [ALA and GLA] scores >median (versus ≤median) were associated with increased odds of breast cancer-specific mortality (OR = 1.42; 95% CI = 1.01–2.01). Additionally, 1-SD increase in Factor 4 scores were associated with ORs of 1.22 (95% CI = 1.04–1.42) for all-cause mortality and 1.24 (95% CI = 1.05–1.47) for breast cancer-specific mortality. Conclusions: RBC PUFA composition profiles are associated with all-cause and breast cancer-specific mortality risk among women with breast cancer.