Erythrocyte fatty acids and risk of endometriosis

项目总结/摘要 子宫内膜异位症是一种常见的妇科疾病， 子宫外的组织它给大约10%的育龄妇女带来负担， 卫生保健费用和发病率，子宫内膜异位症妇女经历不孕症，慢性盆腔疼痛， 痛经和慢性疲劳。这些症状对生活质量有很大影响，但很少 已经确定了可改变的因素，用于降低子宫内膜异位症的风险或改善其症状。 条件 脂肪酸已被假设影响子宫内膜异位症的风险和进展，通过其 可能改变内源性激素及其炎症作用。然而，先前的研究已经 仅使用自我报告的膳食脂肪摄入量，这可能容易导致错误分类。相反， 红细胞脂肪酸（EFA）提供了一种更可靠和生物相关的测量方法， 而不是自我报告。我们的主要目标是调查EFA是否影响子宫内膜异位症的风险。填补重要 在脂肪酸和子宫内膜异位症之间的关联知识的差距，我们将利用护士的健康 研究II是一项对美国女性进行了30多年随访的前瞻性队列研究。这个群体代表了一个独特的 有机会评估EFA与子宫内膜异位症风险之间的关联， 29，611名妇女，其中300例子宫内膜异位症病例和300例对照者将被选择进行巢式 病例对照研究我们还将使用孟德尔随机化方法， 总结性统计，以检查相关性，而不扭曲混杂或反向因果关系。我们 提出以下具体目标/假设： 目标1.我们假设n-3多不饱和脂肪酸（PUFA）的EFA水平较高， 单不饱和脂肪酸（MUFA）和极长链饱和酸（VLCSFAs）与 子宫内膜异位症的风险较低，而高水平的长链饱和脂肪酸与高风险相关。 目标二。我们将使用孟德尔随机化方法来评估遗传变异是否与 PUFA水平与子宫内膜异位症的风险呈负相关。此外，我们还将评估 基因预测的促炎脂肪酸谱与风险相关。 这一提议是理解EFAs与其 与子宫内膜异位症发病率相关。鉴于10%的女性患有子宫内膜异位症， 健康和经济影响巨大。具体来说，这项研究可能是确定一种 子宫内膜异位症及其症状的可改变的危险因素，其中很少存在。

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.