Erythrocyte fatty acids and risk of endometriosis

红细胞脂肪酸与子宫内膜异位症的风险

• 批准号: 10527106
• 负责人: Holly Ruth Harris
• 金额: $ 28.46万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527106
• 关键词: Acids; Affect; Age; Animal Model; Archives; Biological Markers; Blood specimen; Carbon; Chronic; Complement; Coronary heart disease; Diagnosis; Diet; Dietary Factors; Dietary Fats; Dietary intake; Disease; Dysmenorrhea; Endometrial; Erythrocytes; Etiology; Fatigue; Fatty Acids; Fatty acid glycerol esters; Goals; Gynecologic; Health; Health Care Costs; Healthcare; Hormones; In Vitro; Incidence; Infertility; Inflammation; Inflammatory; Intake; Investigation; Knowledge; Length; Measures; Meat; Mendelian randomization; Metabolism; Monounsaturated Fatty Acids; Morbidity - disease rate; N-3 polyunsaturated fatty acid; Nested Case-Control Study; Nurses' Health Study; Pain; Patient Self-Report; Periodicity; Play; Polyunsaturated Fatty Acids; Prospective Studies; Prospective cohort; Prostaglandins; Publishing; Quality of life; Research; Risk; Risk Factors; Role; Saturated Fatty Acids; Smooth Muscle; Subgroup; Symptoms; Tissues; Trans Fats; Trans Fatty Acids; Uterus; Woman; Work; base; case control; chronic pelvic pain; cohort; design; dietary; economic impact; endometriosis; estrogenic; evidence base; experience; genetic variant; health economics; high risk; in vivo; modifiable risk; novel; pain symptom; protective effect; reduce symptoms; reproductive; reproductive outcome; saturated fat; secondary analysis; statistics

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.

项目摘要/摘要 子宫内膜异位症是一种常见的妇科疾病，其特征是存在子宫内膜样 在子宫外面的组织。它燃烧了大约10％的复制年龄妇女，并产生大量 医疗保健成本和发病率，患有子宫内膜异位症的女性不孕，慢性骨盆疼痛， 痛经和慢性疲劳。这些符号对生活质量有重大影响，但很少 已经确定了可修改因素，以降低子宫内膜异位症或改善这种症状 健康）状况。 假设脂肪酸通过其通过其影响子宫内膜异位症的风险和进展 改变内源性恐怖及其炎症作用的潜力。但是，先前的研究已经 仅利用自我报告的饮食脂肪摄入量，可能很容易出现错误分类。相反，生物标志物 红细胞脂肪酸（EFAS）提出了更健壮和与生物学相关的测量 比自我报告。我们的主要目标是研究EFA是否影响子宫内膜异位症的风险。填补重要的 关于脂肪酸与子宫内膜异位症之间关联的知识差距，我们将利用护士的健康 研究II，美国妇女的前瞻性队列跟踪了30多年。这个队列代表了一个独特的 评估EFA与子宫内膜异位症风险与存储的血液样本之间的关联的机会 29,611名妇女，其中300例事件子宫内膜异位症病例和300例将被选为嵌套 病例对照研究。我们还将使用采用公开可用的门德尔随机化方法 摘要统计数据，以检查关联而不会造成混杂或反向偶然性的扭曲。我们 提案以下特定目标/假设： AIM 1。我们假设较高的EFA水平的N-3多不饱和脂肪酸（PUFAS），， 单不饱和脂肪酸（MUFA）和非常长链饱和酸（VLCSFA）与 子宫内膜异位症的风险较低，而较高水平的长链饱和脂肪酸与较高的风险有关。 AIM 2。我们将使用Mendelian随机化方法来评估遗传变异是否相关 PUFA水平与子宫内膜异位症的风险成反比。此外，我们将评估是否 遗传预测的促炎脂肪酸概况与风险有关。 该提议是了解天生与其之间关系的新颖的第一步 与子宫内膜异位的发生率有关。鉴于10％的女性经历了子宫内膜异位症，潜力 健康和经济影响是巨大的。具体而言，这项研究可能是确定一个 子宫内膜异位症及其症状的可修改风险因素，很少有人存在。