Abstract 2260: Non-alcoholic fatty liver disease polygenic risk score and risk of hepatocellular carcinoma in an East Asian population

Abstract Purpose: It is difficult to identify people with non-alcoholic fatty liver disease (NAFLD) who are at high risk for the development of hepatocellular carcinoma (HCC). A polygenic risk score (PRS) for hepatic fat derived from non-Asians has been reported to be associated with HCC risk in European populations. However, population level data of this risk in non-European populations are lacking. Methods: Utilizing resources from the Singapore Chinese Health Study (SCHS), we examined the relationship between the previously published hepatic fat PRS (HFC-PRS) and HCC risk. We also constructed and evaluated a NAFLD-related PRS (NAFLD-PRS); the final version included SNPs in similar gene regions as the HFC-PRS but weighted by effect estimates for NAFLD among those with East Asian ancestry. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of HCC incidence with both HFC-PRS and NAFLD-PRS. Results: The HFC-PRS and NAFLD-PRS were highly correlated (Spearman r = 0.79, P < 0.001). The highest quartiles of both the HFC-PRS and the NAFLD-PRS were associated with significantly increased risk of HCC with HR of 2.39 (95% CI 1.51, 3.78) and 1.77 (95% CI 1.15, 2.73), respectively, compared to their respective lowest quartile. Conclusion: The HFC-PRS and the NAFLD-PRS may both be useful in stratifying Asian populations according to their risk of HCC. In addition, the association between the NAFLD-PRS, derived from East Asians, and HCC risk suggests a potential causal role for NAFLD in the development of HCC in this population. Citation Format: Claire E. Thomas, Brenda Diergaarde, Allison L. Kuipers, Jennifer J. Adibi, Hung N. Luu, Xuling Chang, Rajkumar Dorajoo, Chew-Kiat Heng, Chiea-Chuen Khor, Renwei Wang, Aizhen Jin, Woon-Puay Koh, Jian-Min Yuan. Non-alcoholic fatty liver disease polygenic risk score and risk of hepatocellular carcinoma in an East Asian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2260.