Abstract PO-160: Association between variants in acinar-to-ductal metaplasia genes and pancreatic cancer incidence in racially diverse populations

Abstract Background: Pancreatic cancer is one of the deadliest cancers with increasing incidence and mortality. Racial/ethnic disparities in incidence have been observed in the United States with African Americans exhibited the highest incidence. In the Multiethnic Cohort Study (MEC), we found elevated risk among African Americans, Japanese Americans and Native Hawaiians. Acinar-to-ductal metaplasia (ADM) is considered the main origin of pancreatic pre-neoplastic lesions that eventually develop into pancreatic ductal adenocarcinoma (PDAC). In our preliminary in-vitro study, we found differences in the rate of ADM across racial/ethnic groups with Blacks undergoing ADM greater than whites followed by Hispanics. We hypothesize that genetic variants in genes involved in the ADM process are associated with PDAC risk. Methods: We examined the associations of single nucleotide polymorphisms (SNP) in KRT19, PTF1A and SOX9 with risk of PDAC in two prospective cohorts: the MEC and the Southern Community Cohort Study (SCCS). Nested case-control samples with 691 incident PDAC cases and 13,778 controls from African-American, Japanese- American, Latino, Native Hawaiian, and white participants were included in this analysis. SNP and PDAC associations were examined using logistic regression, adjusting for age, sex, study, body mass index, diabetes, and population stratification using principal components. Results: In racial/ethnic groups combined, no association was observed between SNPs in KRT19, PTF1A and SOX9 and PDAC risk. However, in ethnic-stratified analyses, we found significant associations between PTF1A and PDAC in whites; rs1886763 (G/A) OR=1.72 (95% CI: 1.22, 2.42). We also found significant associations between 7 SNPs in KRT19 and PDAC among Japanese Americans. All these 7 SNPs were in high linkage disequilibrium, with the strongest of these associations was observed for rs56051972 (G/C) OR=1.77 (95% CI 1.17, 2.66). Conclusions: In this racially diverse populations, we found associations between key ADM genes and PDAC risk in certain racial/ethnic groups. Our findings suggest potential role of ADM in influencing PDAC risk. Citation Format: David Bogumil, Thomas Schmittgen, Corey Perkins, Eun-Sook Lee, Mariana Stern, John Carpten, Veronica Wendy Setiawan. Association between variants in acinar-to-ductal metaplasia genes and pancreatic cancer incidence in racially diverse populations [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-160.