Project 1: Molecular and Epidemiologic Heterogeneity and Disparities in Endometrial Cancer Outcomes

Background and Rationale

NC provides an outstanding platform to study disparities in endometrial cancer occurrence and clinical outcomes.
Few epidemiologic and translational studies on endometrial cancer disparities between Non-Hispanic Black and Non-Hispanic White women.
Non-endometrioid carcinomas are more common among Non-Hispanic Black women and appear to be rapidly rising.
In TCGA Non-Hispanic Black women more often had molecular subtypes associated with worse progression-free survival. Specific gene loss (mutation, methylation) has worse survival, but not examined for disparities.
Endometrial cancer disparities examined in the context of established risk factors such as obesity and co-morbid conditions and potential variation in access to care, treatment receipt and patient preferences.
No large population-based molecular epidemiology study with inclusion of Non-Hispanic Black women.
Provide evidence-base for translation to clinical practice and future mechanistic research in a disparities context.

To assess variation in the distribution of EC molecular features and subtypes associated with poor prognosis among Black and White women.
To assess, using latent class analysis, how social determinants, access to care, comorbid conditions, symptom recognition, diagnostic procedures, clinical and tumor characteristics, and cancer treatment interact in EC and to determine variation by race.

NC population-based cohort (2020+).
100 counties, rapid case ascertainment, all endometrial cancer.
Includes ascertainment through all hospitals.
Oversample Non-Hispanic Blacks.
400 cases enrolled per year (200 Non-Hispanic Black, 200 Non-Hispanic White).
About 1,000 (500 Non-Hispanic Black, 500 Non-Hispanic White) with tumor data in three years.

Baseline telephone interview.
Information on obesity, sociodemographic factors, medical history, physical activity, family history, hormone use, other risk factors, access to care.
Collect Oragene saliva kit for DNA.
Consenting.
Consent for release of medical records.
Consent for release of FFPE tumor blocks.
Pilot study: for a patient subcohort (25 Non-Hispanic Black, 25 Non-Hispanic White) in-person visits will be conducted to validate body size and other information and collect microbiome kits.

Follow-up telephone interviews (12, 24 months).
Information on changes in medical history, weight change, sociodemographic factors, physical activity, access to care, financial impact, quality of life.
Medical Records and Outcome Assessment.
Continue acquisition and abstraction of medical records related to diagnosis and treatment. Ascertain recurrence and vital status.
Biospecimen collection.
Acquisition of FFPE tumor blocks.
Molecular subtyping.
Next generation sequencing (800 gene panel) and immunohistochemistry.

No other epidemiologic study has used a population-based multifaceted platform and integrative approach to investigate endometrial cancer disparities. UNC team very experienced in this type of study.
Importantly, we have begun the population-based study using institutional funds and will conduct preliminary sequencing analysis of stored UNC samples.
This project will provide important preliminary analyses integrating tumor biology, access to care and other factors to identify contributors, and potential areas for intervention or development, to address endometrial cancer disparities.
Will be important multidisciplinary resource for future SPORE studies by UNC and other investigators.

Andrew Olshan, PhD
Barbara S. Hulka Distinguished Professor, Epidemiology, UNC-Chapel Hill

Hazel Nichols, MD, PhD
Associate Professor, PhD, MSc, Epidemiology, UNC-Chapel Hill

Victoria Bae-Jump, MD, PhD
Professor, Gynecologic Oncology, UNC-Chapel Hill

Russell Broaddus, MD, PhD
Joe W. & Evelyn M. Grisham Distinguished Professor, Pathology, UNC-Chapel Hill