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

Background: The relationship between erythrocyte membrane fatty acids and p ostmenopausal breast cancer risk was analyzed previously only by retrospect ive studies, which suggested a protective effect of increased saturation in dex (Sf), i.e., the ratio of membrane stearic to oleic acid. We investigate d the relationships in a prospective study of hormones, diet, and prediagno stic 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 measu red as a percentage of total fatty acids. Conditional logistic regression a nalysis evaluated the association between membrane fatty acid composition a nd breast cancer risk. The SI, which is influenced by the activity of the e nzyme delta 9 desaturase (Delta9-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, Th e SI (highest to lowest tertile, OR = 0.29; 95% CI = 0.13 to 0.64) was inve rsely associated with breast cancer risk, The analysis suggested an inverse association between total polyunsaturated fatty acids and breast cancer ri sk, but individual polyunsaturated fatty acids behaved differently. There w as 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 var iables depend on the activity of the enzyme Delta9-d. The dietary, metaboli c, and hormonal factors acting on Delta9-d expression and activity and, the refore, on patterns of fatty acid metabolism, should be further investigate d as possible determinants of breast cancer.