Alcohol consumption does not modify the polygenic risk score-based genetic risk of breast cancer in postmenopausal women

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.
Researchers prospectively studied 5,651 White and Black postmenopausal women in the Atherosclerosis Risk in Communities study. Alcohol intake was assessed by food frequency questionnaire. 313-SNPs polygenic risk score (PRS) was calculated. Breast cancer cases were ascertained primarily by cancer registry linkage through 2015. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for the association of PRS and current ethanol intake with breast cancer, and their interaction. 50.6% were current drinkers, and of them 50.8% drank <1 drink/week and 12.8% drank >7 drinks/week.
Higher PRS was associated with higher breast cancer risk among White (HR1-SD:1.48, 95%CI:1.34-1.65) and Black (HR1-SD:1.15, 95%CI:0.96-1.38) women. Positive associations were not observed between current ethanol intake and breast cancer risk (White, HR13g/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 appeared to be positively associated with risk in drinkers and non-drinkers. There was no evidence of an PRS-ethanol intake interaction in 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, the findings suggest that alcohol drinking does not modify PRS-based genetic risk of breast cancer.
Source: Zhang, M., Ru, M., Zhang, J. et al. Alcohol consumption does not modify the polygenic risk score–based genetic risk of breast cancer in postmenopausal women: Atherosclerosis risk in communities study. Cancer Prevention and Research (Phila) 2024; doi.org/10.1158/1940-6207.CAPR-24-0208