Erythrocyte membrane fatty acids and subsequent breast cancer: A prospective Italian study

Background: The relationship between erythrocyte membrane fatty acids and postmenopausal breast cancer risk was analyzed previously only by retrospective studies, which suggested a protective effect of increased saturation index (SI), i.e., the ratio of membrane stearic to oleic acid. We investigated the relationships in a prospective study of hormones, diet, and prediagnostic breast cancer (the ORDET study) conducted in northern Italy. Methods: A total of 4052 postmenopausal women were followed for an average of 5.5 years; 71 cases of invasive breast cancer were identified. For each case subject, two matched control subjects were chosen randomly from among cohort members. The various fatty acids in erythrocyte membranes were measured as a percentage of total fatty acids. Conditional logistic regression analysis evaluated the association between membrane fatty acid composition and breast cancer risk. The SI, which is influenced by the activity of the enzyme delta 9 desaturase (Δ9-d), was also investigated. All statistical tests were two-sided. Results: Oleic (highest versus lowest tertile of percentage of total fatty acids, odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.24 to 6.28) and monounsaturated fatty acids (highest to lowest tertile, OR = 5.21; 95% CI = 1.95 to 13.91) were positively associated with breast cancer risk. The SI (highest to lowest tertile, OR = 0.29; 95% CI = 0.13 to 0.64) was inversely associated with breast cancer risk. The analysis suggested an inverse association between total polyunsaturated fatty acids and breast cancer risk, but individual polyunsaturated fatty acids behaved differently. There was no association between saturated fatty acids and breast cancer risk. Conclusions: We have found that monounsaturated fats and SI in erythrocyte membranes are predictors of postmenopausal breast cancer. Both of these variables depend on the activity of the enzyme Δ9-d. The dietary, metabolic, and hormonal factors acting on Δ9-d expression and activity and, therefore, on patterns of fatty acid metabolism, should be further investigated as possible determinants of breast cancer.