Abstract A024: Exploring liver cancer risk factors by birth cohort: An electronic health record (EHR)-based epidemiologic cohort study

Abstract Background: Most hepatocellular carcinoma (HCC) cases in the U.S. have been attributed to chronic hepatitis B (HBV) and hepatitis C virus (HCV) infections, though burden of alcoholic liver disease and metabolic-dysfunction associated fatty liver disease (MAFLD) is rising. Individuals born between 1945-1965 (“the baby boomers”), comprise 25% of the U.S. population but account for 81% of chronic HCV infections and thus bear a disproportionate burden of HCC compared to younger or older cohorts. We examined the association of HCV and other risk factors to liver cancer incidence within liver cancer birth cohorts. Methods: Adults with at least one visit from 2000-2017 to San Francisco Health Network (SFHN), Sutter Health Northern California, and Kaiser Permanente Hawai’i (KPH) were linked to data on incident HCC from the California (SFHN/Sutter) and Hawai’i (KPH) cancer registries through 2017. The three birth cohorts were defined as 1)1895-1944 (“pre-baby boomer”); 2)1945-1965 (“baby boomer”); 3)1966-1999 (“post-baby boomer”). We used Cox proportional hazards regression with age as the timescale to examine association of each risk factor (i.e., HBV, HCV, metabolic syndrome, MAFLD, alcohol use, smoking history) with incident HCC stratified by sex and birth cohort; models were adjusted for site, baseline year, number of encounters, length of active follow-up, race/ethnicity, and cirrhosis. For next steps, we plan to calculate the population attributable fraction for each of these risk factors. Results: From the pooled cohort of 4,248,553 individuals, 2,916 had incident HCC. 15% were born between 1895-1944; 32% from 1945-1965; and 53% from 1966-1999; 55% were females; 39% identified as non-Hispanic (NH) White; 14% as Asian American; 11% as Hispanic; 5% as NH Black. Across all birth cohorts, males and females with active chronic hepatitis B had higher HCC risk compared to those with inactive status. Males and females in the pre-baby boomer and baby boomer cohorts (but not post baby-boomers) with active chronic hepatitis C had higher HCC risk. Males and females in the pre-baby boomer cohort (Hazard Ratio [HR]=2.58, 95% Confidence Interval [CI] 2.01-3.31); HR=2.85, 95% CI 2.03-4.00, respectively) and females in the baby boomer cohort (HR=1.55, 95% CI 1.03-2.32) with metabolic syndrome had higher HCC risk. Having MAFLD was associated with increased HCC risk among males from all three birth cohorts and females in the pre-baby boomer and baby-boomer cohort. Alcohol use was associated with higher HCC among pre-baby boomer males (HR=1.23, 95% CI 1,04-1.46) and baby boomer females (HR=1.39, 95% CI 1.10-1.76). Conclusion: In this racially, ethnically, and socioeconomically diverse cohort, HBV is a significant risk factor in HCC risk across birth cohorts for both males and females, while HCV is among older birth cohorts. Consistent with recent studies, MAFLD is a growing cause across birth cohorts. Understanding the contribution of these risk factors and for whom they are most relevant can help identify targets for intervention to reduce liver cancer burden. Citation Format: Janet N. Chu, Aly Cortella, Alison J. Canchola, Pushkar Inamdar, Sixiang Nie, Mai Vu, Ma Somsouk, Michele M. Tana, Caroline A. Thompson, Chanda Ho, Hashem B. El-Serag, Mi-Ok Kim, Mark Segal, Yihe G. Daida, Su-Ying Liang, Scarlett L. Gomez, Mindy C. Derouen, Salma Shariff-Marco. Exploring liver cancer risk factors by birth cohort: An electronic health record (EHR)-based epidemiologic cohort study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A024.