ALDH2 Deficiency and Alcohol Intake in the United States: Opportunity for Precision Cancer Prevention

Area of Science:

• Genetics and Genomics
• Cancer Research
• Public Health

Background:

• Alcoholic beverages and acetaldehyde are known carcinogens.
• A specific genetic variant, aldehyde dehydrogenase 2 (ALDH2, rs671), impairs acetaldehyde metabolism and increases cancer risk.
• ALDH2 deficiency presents a target for precision cancer prevention due to alcohol's modifiable risk factor status.

Purpose of the Study:

• To determine the prevalence of ALDH2 deficiency within a large, diverse US population.
• To analyze alcohol consumption patterns among individuals with ALDH2 deficiency.
• To explore associations between sociodemographic factors and ALDH2 genotype regarding alcohol use.

Main Methods:

• Genotyping for the ALDH2 rs671 variant in 311,290 participants from the All of Us Research Program.
• Analysis of self-reported alcohol consumption data.
• Multivariable analysis to identify factors associated with alcohol consumption behavior in relation to ALDH2 genotype.

Main Results:

• ALDH2 deficiency was significantly more prevalent in Asian individuals (23.5%) compared to other groups (<2.5%).
• A majority of individuals with ALDH2 deficiency (61.2% with one deficient allele, 24.4% with two) reported alcohol consumption, including binge drinking.
• ALDH2 genotype, sex, age, race, education, income, employment, marital status, and country of birth were associated with alcohol consumption.

Conclusions:

• Most individuals with ALDH2 deficiency consume alcohol, with consumption patterns influenced by sociodemographic factors.
• Targeted cancer prevention strategies focusing on ALDH2 deficiency, particularly in Asian American populations, are warranted.