Abstract 2211: ALDH2 deficiency and alcohol intake: Opportunity for precision cancer prevention

Abstract

Abstract Alcoholic beverages and the main metabolite of alcohol, acetaldehyde, are known carcinogens, according to the International Agency for Research on Cancer. Many studies have shown that alcohol consumption is a modifiable risk factor for breast, esophageal, colorectal, and other cancers, and that individuals deficient in metabolizing acetaldehyde are at higher risk for alcohol-associated cancers. A genetic variant in aldehyde dehydrogenase 2 (ALDH2, G>A, rs671), the main enzyme responsible for breaking down acetaldehyde, results in decreased efficiency of ALDH2, or ALDH2 deficiency. This is the most common single genetic variation in humans worldwide, mostly found in some East Asian populations. While having one or both deficient alleles can lead to adverse physical effects when drinking, including facial flushing, nausea, and palpitations, studies done in Asian countries have shown that many affected individuals still consume alcohol, increasing their risk for some cancers. We sought to explore the scope and design of potential intervention in the U.S. by examining alcohol consumption behavior in individuals with and without ALDH2 deficiency within the All of Us Research Program, a current large, diverse, national U.S. cohort. Relationships between self-reported alcohol consumption and sociodemographic factors were examined among 380,845 participants. Genomic data was available for 296,254 of them. Overall, 72.7% of the cohort reported drinking alcohol in the past year, with the majority drinking moderately (≤1 drink/day for women and ≤2 drinks/day for men). Among those who drank, 42.7% reported at least one binge drinking episode (≥6 drinks on one occasion). Among our genomic cohort who identified as Asian individuals, 23.6% had at least one deficient ALDH2 allele compared to <4% in all other groups. 63.7% of individuals with one deficient ALDH2 allele and 25.4% with two deficient ALDH2 alleles reported drinking in the past year. 29.9% of individuals with ALDH2 deficiency reported binge drinking in the past year. Multivariate analysis showed that male sex, younger age, higher education level, higher household income, and being born in the U.S. were associated with alcohol consumption among both individuals with and without ALDH2 deficiency. Our study shows that ALDH2 deficiency is fairly common among Asian Americans and that many affected individuals still drink alcohol. With the growing population of Asian Americans in the U.S. (currently >7% of the total U.S. population, projected to be ~38 million individuals by 2050), our findings suggest a significant opportunity for precision cancer prevention for a substantial portion of the population. Citation Format: Danielle Forman, Manxi Yang, Ryan Chien, Hester Nguyen, Caressa Wong, Jacqueline H. Kim, Argyrios Ziogas, Hannah Lui Park. ALDH2 deficiency and alcohol intake: Opportunity for precision cancer prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2211.