Abstract IA-40: CDKN2A germline rare coding variants and risk of pancreatic cancer in minority populations
Authors: McWilliams Robert 
Published: January 2022

Performing genetic epidemiology studies in underrepresented populations is challenging, but is extremely important in order to understand how cancer impacts differing populations, This can then allow more tailored and nuanced management of persons at risk. Our group at Mayo Clinic encountered some interesting preliminary findings regarding CDKN2A, but given small numbers of subjects in our registry, we needed to partner with other collaborators to have enough statistical power to make sense of the findings and generate a publishable result. This talk will focus on the means of doing this, the importance of team-based science across centers, and future opportunities. Background: Pathogenic germline mutations in the CDKN2A tumor suppressor gene are rare and associated with highly penetrant familial melanoma and pancreatic cancer in non-Hispanic whites. WeTo date, the prevalence and impact of CDKN2A rare coding variants (RCV) in racial minority groups remain poorly characterized. We examined the role of CDKN2A RCVs on the risk of pancreatic cancer among minority subjects. Methods: We performed a case-control study of germline mutations in CDKN2A among patients with incident pancreatic cancer and controls, focused on underrepresented minority populations. We sequenced CDKN2A in 220 African American pancreatic cancer cases, 900 noncancer African American controls, and 183 Nigerian controls. RCV frequencies were determined for each group and compared with that of 1,537 Non-Hispanic White patients with pancreatic cancer. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for both a case–case comparison of RCV frequencies in African Americans versus Non-Hispanic Whites, and case–control comparison between AA cases versus noncancer AA controls plus Nigerian controls. Smaller sets of Hispanic and Native American cases and controls also were sequenced. Race/ethnicity categorization was from self-report. Results: One novel missense RCV and one novel frameshift RCV were found among AA patients: 400G&gt;A and 258_278del. RCV carrier status was associated with increased risk of pancreatic cancer among AA cases (11/220; OR, 3.3; 95% CI, 1.5–7.1; P ¼ 0.004) compared with African American and Nigerian controls (17/1,083). Further, African American cases had higher frequency of RCVs: 5.0% (OR, 13.4;95%CI, 4.9–36.7; P &lt; 0.001) compared with Non-Hispanic White cases (0.4%). Conclusions: CDKN2A RCVs are more common in African Americans than in Non-Hispanic White patients with pancreatic cancer and associated with moderately increased pancreatic cancer risk among African Americans.

Citation Format: Robert McWilliams. CDKN2A germline rare coding variants and risk of pancreatic cancer in minority populations [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA-40.