Alcohol Consumption Does not Modify the Polygenic Risk Score–Based Genetic Risk of Breast Cancer in Postmenopausal Women: Atherosclerosis Risk in Communities Study

High genetic risk and alcohol consumption ≥1 drink/ day are associated with increased breast cancer risk. However, the interaction between alcohol and genetics on breast cancer risk is poorly understood, including in populations not enriched with daily drinkers. We prospectively studied 5,651 White and Black postmenopausal women in the Atherosclerosis Risk in Communities study. Alcohol intake was assessed by a food frequency questionnaire. The 313-SNP polygenic risk score (PRS) was calculated. Breast cancer cases were ascertained primarily by cancer registry linkage through 2015. Multivariable Cox regression was used to estimate HRs and 95% confidence intervals (CI) for the association of PRS and current ethanol intake with breast cancer, and their interaction. Of these individuals, 50.6% were current drinkers, and of them, 50.8% drank <1 drink/week and 12.8% drank >7 drinks/week. A higher PRS was associated with a higher breast cancer risk among White (HR_1-SD, 1.48; 95% CI, 1.34–1.65) and Black (HR_1-SD, 1.15; 95% CI, 0.96–1.38) women. Positive associations were not observed between current ethanol intake and breast cancer risk (White: HR_{13 g/week} 1.00; 95% CI, 0.98–1.03; Black: HR, 0.83; 95% CI, 0.69–1.00). Among both White and Black women, PRS generally seemed to be positively associated with risk in drinkers and nondrinkers. There was no evidence of a PRS–ethanol intake interaction among White or Black women. Patterns in Black women were similar when using an 89-SNP PRS developed among African ancestry women. In conclusion, in a prospective analysis of White and Black postmenopausal women in a study population not enriched with daily drinkers, our findings suggest that alcohol drinking does not modify the PRS-based genetic risk of breast cancer.