Plasma Phospholipid Fatty Acids and Breast Cancer Risk in Alberta’s Tomorrow Project

Abstract

Abstract Objectives It is estimated that lifestyle factors, such as dietary intake, contribute up to 21% of all breast cancer (BC) cases. High dietary intakes of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) have been associated with a reduced incidence of BC. Dietary intake of n-3 LCPUFA typically correlate with blood fatty acid concentrations, but the relationship between blood fatty acid concentrations and BC risk has not yet been established. We hypothesized that higher plasma phospholipid (PL) content of n-3 LCPUFAs would be associated with a reduced risk of BC. Methods Plasma samples and relevant covariables were obtained from 614 age-matched women (203 with BC/411 control) from a nested case-control within Alberta's Tomorrow Project. PL fatty acid concentration and relative % composition were determined from baseline plasma samples (collected 9–16 years pre-BC diagnosis). Principal component analysis was employed to determine predictive models for fatty acid clusters. Conditional logistic regression models controlled for covariates were used to assess the relative risk of BC (odds ratio-OR) by fatty acid content. Sub-group analyses by menopausal status and BMI at baseline were also performed. Results When adjusted for BMI and menopausal status, individual fatty acids, including linoleic acid (OR = 1.75, 95% confidence interval (CI) = 1.08,2.84, P < 0.04) and arachidonic acid (OR = 1.60, 95% CI = 1.03,2.49, P < 0.04), were positively associated with BC risk. However, composite analysis of grouped fatty acids were found to be stronger indicators of risk – total PUFA (µg/mL; OR = 2.25, 95% CI = 1.4,3.44, P < 0.001), total n-6 PUFA (OR = 2.11, 95% CI = 1.32,3.36, P < 0.002), and total n-3 PUFA (OR = 1.57, 95% CI = 1.06,2.32, P < 0.02), were independent predictors of BC risk. Conclusions In contrast to epidemiological dietary evidence, this study found an increased risk of BC with higher plasma concentrations of n-3 LCPUFA. However, the absolute n-3 concentration in this population was low, and therefore a second cohort is being assessed to validate these results. Overall, this study suggests that risk of BC cannot be predicted by isolated fatty acid blood concentrations, but that the balance of different fatty acids or the combination of n-3 and n-6 fatty acids may be a better predictor of BC. Funding Sources Funded by Women and Children's Health Research Institute.