Erythrocyte fatty acids and risk of endometriosis

项目摘要/摘要 子宫内膜异位症是一种常见的妇科疾病，其特征是子宫内膜样变。 子宫外的组织。它给大约10%的育龄妇女造成了负担，并导致显著的 医疗费用和发病率，患有子宫内膜异位症的妇女经历不孕不育，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。 已经确定了可以降低子宫内膜异位症风险或改善其症状的可修改因素 条件。 已有假说认为，脂肪酸通过其受体影响子宫内膜异位症的风险和进展 有可能改变内源性激素及其炎症效应。然而，先前的研究已经 仅使用自我报告的膳食脂肪摄入量，这可能容易产生错误分类。相反，生物标记物 红细胞脂肪酸(EFAs)是一种更可靠、更具生物相关性的测量方法，它提供了更丰富的信息 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。填补重要的空白 关于脂肪酸与子宫内膜异位症之间关系的知识差距，我们将利用护士的健康 研究二，对美国女性的预期队列进行了30多年的跟踪调查。这一群体代表着一种独特的 利用储存的血液样本评估EFA与子宫内膜异位症风险的相关性 29,611名妇女，其中300名发生子宫内膜异位症病例和300名对照将被选为嵌套 病例对照研究。我们还将使用孟德尔随机化方法，该方法利用公共可用 汇总统计数据，在不扭曲混淆或反向因果关系的情况下检查关联。我们 提出以下具体目标/假设： 目的1.我们假设n-3多不饱和脂肪酸(PUFA)的全民教育水平较高， 单不饱和脂肪酸(MUFAs)和超长链饱和酸(VLCSFAs)与 子宫内膜异位症的风险较低，而长链饱和脂肪酸水平较高与风险较高相关。 目的2.我们将使用孟德尔随机化方法来评估遗传变异是否与 多不饱和脂肪酸水平与子宫内膜异位症的风险呈负相关。此外，我们会评估一个 基因预测的致炎脂肪酸谱与风险相关。 这一建议是朝着理解EFA和它们之间的关系迈出的第一步 与子宫内膜异位症发病率的关系。鉴于10%的女性患有子宫内膜异位症，潜在的 对健康和经济的影响是巨大的。具体地说，这项研究可能是确定一个 子宫内膜异位症及其症状的可改变的危险因素，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.