Abstract SY38-02: Epigenetics, ancestry, and cancer disparities: When nature might be nurture

Abstract Despite an overall decrease in cancer mortality, survival disparities between racial and ethnic groups stubbornly persist. Black patients have the highest all-cancer mortality rate in the US, including common breast, colon, lung, and prostate cancer types, even though Whites show the highest overall rate of new cancer cases. We conducted an analysis of survival disparities of 33 cancers for 9,818 patients using the NCI Cancer Genome Atlas. We identified four cancer types with significant cancer survival disparities between racial and ethnic groups - breast invasive carcinoma, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma, and skin cutaneous carcinoma - along with seven cancer-related genes that interact with genetic ancestry to contribute to the observed disparities. I highlight the implications of our results pointing to epigenetic mechanisms, DNA methylation in particular, as a link between genetic (nature) and environmental (nurture) contributions to cancer health disparities. We found that genetic differences between groups could not explain the disparities we observed. There were, however, clear differences in group-specific patterns of DNA methylation and gene expression that were associated with cancer survival disparities. For example, hypomethylation of the PAQR6 gene promoter region in African ancestry patients is associated with higher gene expression and a greater risk of breast cancer mortality compared to European ancestry patients. These results suggest that changes in gene expression mediated by epigenetic mechanisms have a greater contribution to cancer survival disparities than group-specific genetic variants, consistent with a previously proposed role for epigenetics in health disparities. Citation Format: I. King Jordan. Epigenetics, ancestry, and cancer disparities: When nature might be nurture [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr SY38-02.