A pooled analysis of dietary long-chain omega-3 fatty acid intake and endometrial cancer risk

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ABSTRACT Endometrial cancer is the most common gynecologic malignancy in the United States and the fourth most common cancer diagnosed in women. Incidence of the disease is rising, especially among black women who tend to be diagnosed with aggressive disease and who have a disproportionally higher mortality rate. Coupled with very low research funding on a per case and per death basis relative to other female cancers, and with few modifiable risk factors for disease prevention, there is a critical need to better understand endometrial cancer etiology, with special attention to racial disparities. There is increasing evidence that inflammation is an important driver of endometrial carcinogenesis. Long- chain omega-3 polyunsaturated fatty acids (LCn3PUFA) are anti-inflammatory and have been shown by us to reduce endometrial cancer risk. However, we have reported differences in these associations by body mass and tumor histology. No study has been able to examine whether the association between diets high in LCn3PUFA and endometrial cancer risk differs between black and white women. In order to reveal reliable estimates of association and to identify subgroups of women that stand to benefit the most from diets rich in LCn3PUFA, a very large study is needed. We propose to examine the association of dietary LCn3PUFA with endometrial cancer and its subtypes and to examine possible heterogeneity of these associations by race and body mass, by pooling dietary data in the Epidemiology of Endometrial Cancer Consortium of studies. This secondary analysis will include 19 participating studies, 10,117 endometrial cancer cases and 26,881 controls, and will provide high statistical power and precision to examine these research questions. The proposed work will have a significant impact on endometrial cancer prevention by informing clinicians, patients, and nutrition scientists as to whether and for whom an LCn3PUFA-rich diet may be of benefit. Results from this investigation will inform a larger NIH grant application to conduct a chemoprevention trial that will aim to examine whether LCn3PUFA supplementation increases LCn3PUFA concentrations and causes a reduction in biomarkers of inflammation in endometrial tissues of women diagnosed with endometrial cancer. Our long-term goal is to reduce incidence among high- risk women, such as those diagnosed with endometrial hyperplasia, and to reduce recurrence among endometrial cancer survivors.