BackgroundModerate to heavy alcohol consumption is associated with an increased risk of breast cancer. The etiologic role of genetic variation in genes involved in ethanol metabolism has not been established, with little information available among women of African ancestry.MethodsOur analysis from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium included 2889 U.S. Black women who were current drinkers at the time of breast cancer diagnosis (N cases = 715) and had available genetic data for four ethanol metabolism genomic regions (ADH, ALDH, CYP2E1, andALDH2). We used generalized estimating equations to calculate genetic effects, gene* alcohol consumption (≥ 7drinks/week vs. < 7/week) interactions, and joint main plus interaction effects of up to 23,247 variants in ethanol metabolism genomic regions on odds of breast cancer.ResultsAmong current drinkers, 21% of cases and 14% of controls reported consuming ≥ 7 drinks per week. We identified statistically significant genetic effects for rs79865122-C inCYP2E1with odds of ER- breast cancer and odds of triple negative breast cancer, as well as a significant joint effect with odds of ER- breast cancer (≥ 7drinks per week OR = 3.92, < 7 drinks per week OR = 0.24,pjoint= 3.74 × 10−6). In addition, there was a statistically significant interaction of rs3858704-A inALDH2with consumption of ≥ 7 drinks/week on odds of triple negative breast cancer (≥ 7drinks per week OR = 4.41, < 7 drinks per week OR = 0.57,pint= 8.97 × 10–5).ConclusionsThere is a paucity of information on the impact of genetic variation in alcohol metabolism genes on odds of breast cancer among Black women. Our analysis of variants in four genomic regions harboring ethanol metabolism genes in a large consortium of U.S. Black women identified significant associations between rs79865122-C inCYP2E1and odds of ER- and triple negative breast cancer. Replication of these findings is warranted.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13058-023-01660-1.