Zhang Minghui, Ru Meng, Zhang Jingning, Wang Ziqiao, Lu Jiayun, Butler Kenneth R, Chatterjee Nilanjan, Couper David J, Prizment Anna E, Soori Mehrnoosh M, Visvanathan Kala, Zahnow Cynthia A, Joshu Corinne E, Platz Elizabeth A
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Cancer Prev Res (Phila). 2025 Feb 3;18(2):73-83. doi: 10.1158/1940-6207.CAPR-24-0208.
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 (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: HR13 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. Prevention Relevance: Although our findings suggest that alcohol drinking does not modify the PRS-based genetic risk of breast cancer among White and Black women with lower alcohol intake, nevertheless, women should consider limiting alcohol consumption as a general cancer prevention strategy, as indicated in dietary guidelines.
高遗传风险以及每日饮酒量≥1杯与乳腺癌风险增加相关。然而，酒精与基因在乳腺癌风险方面的相互作用仍知之甚少，在并非以每日饮酒者为主的人群中亦是如此。我们在社区动脉粥样硬化风险研究中对5651名绝经后白种和黑种女性进行了前瞻性研究。通过食物频率问卷评估酒精摄入量。计算313个单核苷酸多态性（SNP）的多基因风险评分（PRS）。主要通过与癌症登记处的关联确定截至2015年的乳腺癌病例。采用多变量Cox回归来估计PRS和当前乙醇摄入量与乳腺癌关联的风险比（HR）及95%置信区间（CI），以及它们之间的相互作用。在这些个体中，50.6%为当前饮酒者，其中50.8%每周饮酒量<1杯，12.8%每周饮酒量>7杯。较高的PRS与白种女性（HR每标准差增加1，1.48；95%CI，1.34 - 1.65）和黑种女性（HR每标准差增加1，1.15；95%CI，0.96 - 1.38）中较高的乳腺癌风险相关。未观察到当前乙醇摄入量与乳腺癌风险之间存在正相关（白种女性：HR每周13克，1.00；95%CI，0.98 - 1.03；黑种女性：HR，0.83；95%CI，0.69 - 1.00）。在白种和黑种女性中，PRS在饮酒者和不饮酒者中似乎通常都与风险呈正相关。没有证据表明白种或黑种女性中存在PRS - 乙醇摄入量的相互作用。当使用在非洲裔女性中开发的89个SNP的PRS时，黑种女性中的模式相似。总之，在一个并非以每日饮酒者为主的研究人群中对白种和黑种绝经后女性进行的前瞻性分析中，我们的研究结果表明饮酒不会改变基于PRS的乳腺癌遗传风险。预防意义：尽管我们的研究结果表明白种和黑种且饮酒量较低的女性中饮酒不会改变基于PRS的乳腺癌遗传风险，但正如饮食指南中所指出的，女性仍应考虑限制饮酒作为一项一般的癌症预防策略。
