The impact of environmental factors and social determinants of health on molecular alterations in a single-center endometrial cancer cohort.

Abstract

e17634 Background: Molecular classification has become increasingly important in endometrial cancer (EC) management. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identifies four EC subgroups: POLE mutated, mismatch repair (MMR) deficient, p53 abnormal (p53abn), and No Specific Molecular Profile (NSMP), each with prognostic and treatment implications. While environmental exposures are known to influence tumor epigenetics, their relationship with molecular alterations in EC remains unclear. This study evaluated associations between air quality measured by fine particulate matter (PM2.5), social vulnerability (SV), environmental justice (EJ), and EC molecular alterations. Methods: Newly diagnosed EC patients at a single academic institution from 1/1/2018-12/31/2021 were identified retrospectively. Demographic and clinicopathologic data were obtained through electronic medical records. Annual census tract level median PM2.5 was derived from the Environmental Protection Agency (EPA). SV and EJ index variables were obtained from the Centers for Disease Control and Prevention (CDC). The relationship between MMR, microsatellite instability (MSI), and p53 status and SV, EJ, and PM2.5 were evaluated using t-tests and Pearson’s chi-square tests. Results: Among 330 identified patients, the mean age was 62.3. Most were obese (72.7%), non-smokers (55.7%), and had stage I disease (56.7%). Black patients comprised 43% of the cohort. Low-grade histology comprised 47% of tumors. When MMR status was known, the majority were MMR proficient (68.2%), while 31.8% were MMR deficient. When MSI status was known, 70.7% were microsatellite stable and 29.3% demonstrated microsatellite instability. P53 status was known in only 42% of patients, of which 53.2% were p53abn. POLE status was not routinely tested. MMR, MSI, and p53 status were associated with histology and tumor grade (p < 0.001). P53 status was associated with EC stage (p=0.001). PM2.5 was associated with tumor grade (χ², p=0.013) and p53 status (χ², p=0.014), but not MMR or MSI status in this cohort. These molecular alterations were not associated with SV, EJ, population density, or other patient-level factors. Conclusions: Census tract level PM2.5 was associated with tumor grade and p53 status in EC, but not MMR or MSI status. A better understanding of the relationship between air quality and epigenetic changes associated with EC is warranted.