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Erythrocyte fatty acids and risk of endometriosis

红细胞脂肪酸与子宫内膜异位症的风险

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目总结/文摘