The 6:3 PUFA ratio and serum estradiol in postmenopausal women Free

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Background: Although omega-6 polyunsaturated fatty acids (PUFAs) have been demonstrated to promote breast tumorigenesis and omega-3 PUFAs have been found to prevent breast cancer, the exact mechanisms are unknown. In vitro studies suggest that these two families of fatty acids influence breast cancer risk by impacting eicosanoid synthesis. In particular, when omega-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), displace omega-6 arachidonic acid (AA), prostaglandin E2 synthesis (PGE2) is reduced, thus resulting in decreased aromatase activity, and ultimately suppression of estrogen biosynthesis. Based on these laboratory observations, we sought to determine whether the ratio of AA:EPA+DHA in red blood cells (RBC) is positively associated with serum estradiol concentrations in postmenopausal women. Methods: Participants in this cross-sectional analysis included 260 cancer-free postmenopausal controls enrolled in the Mammograms and Masses Study (MAMS), a case-control study in Pittsburgh, PA. Only participants not taking hormone therapy, antiestrogens or corticosteroids at blood draw were included in the present analysis. RBC fatty acids were measured by gas chromatography. Estradiol was measured in serum using an indirect radioimmunoassay, and values were logarithmically transformed to obtain normal frequency distributions. Pearson’s correlation coefficients were calculated toexamine the relationship between the AA:EPA+DHA ratioand serum estradiol. Partial correlationwas also performed to control for the effects of age and body mass index (BMI). Results: The sample had a mean±SD serum estradiol concentration of 27.1±25.2 pmol/L, BMI of 29.4±7.1, age of 62.7±8.4 years, and was primarily Caucasian (93.1%). Among all 260 participants, the AA:EPA+DHA ratio was positively and significantly correlated with serum estradiol (r=0.25; p<0.001) and remained significant after adjustment for age and BMI (r=0.19; p=0.002). Because anti-inflammatory drugs inhibit AA metabolism and PGE2 formation, separate analyses were performed for participants reporting anti-inflammatory drug use within 48 hours of blood draw and for those not taking these drugs (120 nonusers and 140 users). Adjusting for age and BMI, the AA:EPA+DHA ratio was significantly associated with estradiol among nonusers(r=0.31; p<0.001). However, there was no significant association among the subgroup taking anti-inflammatory drugs (r=0.08; p=0.35). Conclusions: To our knowledge, this is the first study to report on the association between the AA:EPA+DHA ratio in RBC and serum estradiol in postmenopausal women. Our results suggest that among women not using anti-inflammatory agents, increasing intake of the long chain omega-3 PUFAs, EPA and DHA, and reducing intake of the omega-6 PUFA, AA, may result in decreased estradiol production and potentially breast cancer risk. Further research is needed to confirm these findings.