Abstract B061: Nonalcoholic fatty liver disease (NAFLD) polygenic risk score and risk of hepatocellular carcinoma in a multiethnic population

Abstract

Abstract Purpose: Hepatocellular carcinoma (HCC) is the third cause of cancer mortality globally, with 10%-12% of cases attributable to nonalcoholic fatty liver disease (NAFLD). Genetic variants included in NAFLD polygenic risk scores (PRS) have been associated with HCC risk. Since these associations have been studied primarily among European ancestry populations, in the current study we assessed the transportability of a NAFLD PRS associated with HCC risk in a racially/ethnically diverse population. Methods: We conducted a nested case-control study including 275 incident HCC cases and 73,045 controls from the Multiethnic Cohort Study, using a 21-variant PRS for NAFLD created based on prior GWAS and replication studies on MEC participants and other populations. Associations between PRS (per standard deviation) and HCC were estimated using logistic regression adjusting for age, sex, and global ancestry. A stratified analysis was conducted by body mass index (BMI) due to the direct relationship of obesity with NAFLD and HCC. Results: The PRS was associated with HCC risk in the combined sample (ORper SD= 1.84, 95% CI: 1.64-2.06). Signifcant associations were observed in Japanese Americans [ORper SD=2.26 (1.87-2.72)], Latinos [ORper SD=1.89 (1.52-2.35)], Native Hawaiians [ORper SD=1.84 (1.26-2.69)], and with the associations being weaker and non-significant in whites [ORper SD=1.33 (0.92-1.93)] and African Americans [ORper SD=1.25 (0.90-1.75)]. The PRS association was stronger among those with BMI >= 25 kg/m2 for the combined sample (ORper SD :2.46, 95% CI:1.92-3.14), (P heterogeneity <0.0001); and all racial/ethnic groups [Latino: 3.01(1.88-4.81), African American: 2.72 (95% CI: 1.18-6.27), Hawaiian: 2.25 (1.17-4.32), Japanese: 2.13 (1.36-3.36), and White:2.11(1.10-4.04)]. Conclusion: A NAFLD PRS is applicable for HCC risk prediction across racial/ethnic populations. BMI may modifiy this PRS-HCC risk association. Citation Format: Homa Sadeghi, David Bogumil, David V. Conti, Christopher Haiman, Loïc Le Marchand, Veronica Wendy Setiawan. Nonalcoholic fatty liver disease (NAFLD) polygenic risk score and risk of hepatocellular carcinoma in a multiethnic population [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B061.