Erythrocyte fatty acids and risk of endometriosis

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Endometriosis is a common gynecologic disorder characterized by the presence of endometrial-like tissue outside of the uterus. It burdens approximately 10% of reproductive age women and incurs significant health care costs and morbidity, with women with endometriosis experiencing infertility, chronic pelvic pain, dysmenorrhea, and chronic fatigue. These symptoms have a substantial impact on quality of life, yet very few modifiable factors have been identified for reducing risk of endometriosis or ameliorating the symptoms of this condition. Fatty acids have been hypothesized to influence the risk and progression of endometriosis through their potential to modify endogenous hormones as well as their inflammatory effects. However, prior research has utilized only self-reported dietary fat intake, which may be prone to misclassification. Instead, biomarkers of erythrocyte fatty acids (EFAs) present a more robust and biologically-relevant measure that is more informative than self-report. Our primary goal is to investigate whether EFAs influence risk of endometriosis. To fill important gaps in knowledge of the association between fatty acids and endometriosis, we will utilize the Nurses’ Health Study II, a prospective cohort of U.S. women followed for over 30 years. This cohort represents a unique opportunity to evaluate the association between EFAs and endometriosis risk with stored blood samples for 29,611 women from which 300 incident endometriosis cases and 300 controls that will be selected for a nested case-control study. We will also using a Mendelian randomization approach that leverages publicly available summary statistics to examine the associations without the distortion of confounding or reverse causality. We propose the following specific aims/hypotheses: Aim 1. We hypothesize that higher EFA levels of n-3 polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and very-long-chain saturated acids (VLCSFAs) are associated with lower risk of endometriosis while higher levels of long-chain saturated fatty acids are associated with higher risk. Aim 2. We will use a Mendelian randomization approach to assess whether genetic variants associated with PUFA levels are inversely associated with risk of endometriosis. Further, we will assess whether a genetically predicted pro-inflammatory fatty acid profile is associated with risk. This proposal is a novel first-step towards understanding the relationship between EFAs and their association with endometriosis incidence. Given that 10% of women experience endometriosis, the potential health and economic impact is substantial. Specifically, this research may be the first step towards identifying a modifiable risk factor for endometriosis and its symptoms, of which very few exist.