Erythrocyte fatty acids and risk of endometriosis - 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.
