Investigation of socio-genomic associations related to survivial among a population-based sample of those diagnosed with endometrial cancer in Metropolitan Detroit - Among women with endometrial cancer, certain high-risk populations have up to twice the mortality rate compared to others. This is due to a combination of social and biological factors, including socioeconomic differences, histologic subtype, stage at diagnosis, and access to quality care. Some high-risk populations have higher rates of aggressive histologic (e.g., non-endometrioid) and molecular (e.g., P53 abnormal) subtypes of endometrial cancer compared to others but tend to have worse survival across histologic subtypes. Recent studies have demonstrated that a substantial proportion of the excess risk of death experienced by high-risk populations similar to those in Detroit, Michigan cannot be explained by known social and biological factors, underscoring an urgent need for additional research. Chronic stress, through both environment and sociodemographic stressors, is thought to be associated with cancer development, progression, and survival. We hypothesize that chronic stress may modify the relationship between molecular subtypes of endometrial cancer and survival. We have assembled a team of population scientists, bioinformatics researchers, basic scientists, and clinicians to investigate this hypothesis among a cohort of women with endometrial cancer in Metropolitan Detroit. Our preliminary data demonstrated that among women with endometrial cancer, area-based disadvantage measures, which have been shown to correlate with chronic stress, are associated with both overall- and endometrial cancer-specific survival. For this project, we will leverage a comprehensive dataset from the population-based Detroit Research on Cancer Survivors (Detroit ROCS) cohort. This dataset includes annual survey data, geocoded addresses, and longitudinal clinical and vital statistics data for 320 women with endometrial cancer living in Metropolitan Detroit at diagnosis. Additionally, it includes whole exome sequencing of paired normal and tumor biospecimens from 132 women from the Detroit ROCS cohort. Aim 1 will evaluate differences among clinically important molecular characteristics of tumors and associations with survival. In Aim 2, we will investigate associations between chronic stress, molecular characteristics, and survival among the cohort. Aim 3 will involve data collection of a pilot cohort of women with aggressive endometrial cancer from the gynecologic oncology clinics at Karmanos Cancer Institute in Detroit, Michigan, to inform feasibility of the development of a prospective collection of stress measures, molecular characteristics, and endometrial cancer-relevant outcomes in support of a future R01 submission. Collectively, this project aims to generate preliminary data on socio-genomic associations associated with endometrial cancer outcomes, furthering the field of research in improving outcomes for those with gynecologic cancers.
