Project 1: Social-Environmental Measures, Epigenetic Age and Endometrial Cancer Disparities

Univ Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Abstract

PROJECT ABSTRACT – PROJECT 1 Endometrial cancer (EC) is the 4th most common cancer in US women. EC is plagued by a significant cancer health disparity in survival outcomes between Black and White persons; Black women show a two-fold higher incidence of mortality from this cancer. Several putative causes for this disparity have been proposed including a higher risk for more lethal tumor histologies (serous) and molecular subtypes (TP53 mutations) and greater rates of obesity and diabetes. However, these features alone do not account for the full disparity in EC outcomes, suggesting additional factors are involved. We anticipate that measurable social and environmental factors that have been linked to poorer health outcomes account for a significant proportion of EC survival disparities. Specifically, we anticipate that social and environmental exposures act through epigenetic age acceleration to influence endometrial tumor characteristics, and that individual modifiable psychosocial characteristics may influence these relationships. Our overarching hypothesis is that exposure to measurable social and environmental factors increases likelihood of accelerated biological aging, that individual modifiable psychosocial characteristics differentially influence pace of aging, and that accelerated aging will be associated with tumor characteristics and EC outcome. To understand the relationships among DNAm and cancer health disparities in EC, we will identify the global and site-specific differences in DNAm from ECs from Black and White women in the CECS (Carolina Endometrial Cancer Study), a novel North Carolina-based population-based resource. We propose three specific aims: Aim 1. Investigate the associations among measurable social and environmental factors and tumor-based epigenetic age; Aim 2. Investigate the association between psychosocial factors and tumor-based epigenetic age; Aim 3. Examine whether tumor-based epigenetic age predicts EC tumor characteristics, recurrence, and survival. Our results may improve outcomes for EC patients by leading to the identification of modifiable factors that reduce cancer risk.