ALDH2 deficiency and alcohol intake in the U.S.: Opportunity for precision cancer prevention.

Background: Alcoholic beverages and the main metabolite of alcohol, acetaldehyde, are known carcinogens. A genetic variant in aldehyde dehydrogenase 2 (ALDH2, G>A, rs671) leads to decreased efficiency in metabolizing acetaldehyde and is associated with increased cancer risk. Since alcohol consumption is a modifiable risk factor for various cancers, the identification of ALDH2 deficiency presents an opportunity for precision cancer prevention.

Methods: Our primary objectives were to examine the prevalences of ALDH2 deficiency and alcohol consumption behavior among affected individuals within a large, diverse U.S. national cohort. The prevalence of ALDH2 deficiency was determined by examining rs671 genotype among 311,290 participants within the All of Us Research Program. Relationships between self-reported alcohol consumption, sociodemographic factors, and rs671 genotype were analyzed.

Results: ALDH2 deficiency was most prevalent among individuals who identified as Asian, among whom 23.5% had at least one deficient ALDH2 allele compared to <2.5% in all other racial/ethnic groups. Among those with one and two deficient ALDH2 alleles, 61.2% and 24.4% reported drinking in the past year, respectively, and of these, 30.3% and 16.0% reported binge drinking. Multivariable analysis showed that ALDH2 genotype, sex, age, race, education, income, employment, marital status, and country of birth were associated with alcohol consumption behavior.

Conclusions: Most individuals with ALDH2 deficiency reported drinking alcohol in the past year, and consumption was associated with various sociodemographic variables, particularly sex, age, and country of birth.

Impact: Our findings suggest a significant opportunity for precision cancer prevention targeting the unique prevalence of ALDH2 deficiency among Asian Americans.