Abstract 6124: A comprehensive pan-cancer study nominating NF-κB-mediated TNFA signaling-induced hypoxia as a risk factor in Hispanic cancer progression

Abstract The Hispanic (HA) population is the second largest racial/ethnic group in the United States after non-Hispanic White (NHW). Though the HA population usually has a lower reported incidence of cancers compared to NHW, there are racial disparities exist in the mortality rate of some of the cancers. Factors related to the Social Determinants of Health (SDOH), such as higher poverty rates, less education, and reduced access to health care, are known to increase the risk of diagnosing advanced-stage cancer in HA compared to the NHW population. The contribution of such SDOH in the HA cancer population has been studied in the past years. However, the contribution of biological and genetic mechanisms to HA cancer disparity has not been well understood. Thus, in this study, we performed a comprehensive analysis of different databanks to understand the common genetic and biological factors that contribute to the pan-cancer disparity in the HA population. To identify HA and NHW populations, we used self-reported racial/ethnic information. Analysis of the “All of Us” database suggested a high prevalence of infection-related cancers such as Liver, Stomach, and Cervix Uteri in the HA population compared to the NHW population. SEER database also showed an increased percentage of diagnoses with infection-related cancers and poor survival of the HA population with these cancers compared to the NHW. We then analyzed the TCGA transcriptome data from primary tumors from HA and NHW patients. We only selected cancers with data from at least ten patients in each group. TCGA data confirmed that the tumors from HA cancer patients primarily express high inflammatory and immune-responsive signatures. Specifically, we found a high enrichment of NF-κB induced TNFA signaling in HA tumors. We also observed a significant correlation between TNFA and Hypoxia signature in many HA cancers. Since hypoxia is known to be associated with resistance to radiation and chemotherapy, targeting the increased hypoxia signature in HA tumors may be critical for sensitizing HA patients to cancer therapy. Overall, our pan-cancer analyses suggest an increased prevalence of many infection-related cancers in the HA population. HA tumors are enriched with TNFA, NF-κB, and hypoxic signatures. Specific targeting of these signatures may be critical in managing the HA patients who currently suffer from racial disparity in cancer incidence and survival. Citation Format: Tagari Samanta, Jun Hyoung Park, Benny Abraham Kaipparettu. A comprehensive pan-cancer study nominating NF-κB-mediated TNFA signaling-induced hypoxia as a risk factor in Hispanic cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6124.