BACKGROUND Alcohol consumption and cigarette smoking are associated with an increased risk of breast cancer (BC), but it is unclear whether these associations vary by a woman's familial BC risk. METHODS Using the Prospective Family Study Cohort, we evaluated associations between alcohol consumption, cigarette smoking, and BC risk. We used multivariable Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (CI). We examined whether associations were modified by familial risk profile (FRP), defined as the 1-year incidence of BC predicted by Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), a pedigree-based algorithm. RESULTS We observed 1009 incident BC cases in 17,435 women during a median follow-up of 10.4 years. We found no overall association of smoking or alcohol consumption with BC risk (current smokers compared with never smokers HR 1.02, 95% CI 0.85-1.23; consuming ≥ 7 drinks/week compared with non-regular drinkers HR 1.10, 95% CI 0.92-1.32), but we did observe differences in associations based on FRP and by estrogen receptor (ER) status. Women with lower FRP had an increased risk of ER-positive BC associated with consuming ≥ 7 drinks/week (compared to non-regular drinkers), whereas there was no association for women with higher FRP. For example, women at the 10th percentile of FRP (5-year BOADICEA = 0.15%) had an estimated HR of 1.46 (95% CI 1.07-1.99), whereas there was no association for women at the 90th percentile (5-year BOADICEA = 4.2%) (HR 1.07, 95% CI 0.80-1.44). While the associations with smoking were not modified by FRP, we observed a positive multiplicative interaction by FRP (pinteraction = 0.01) for smoking status in women who also consumed alcohol, but not in women who were non-regular drinkers. CONCLUSIONS Moderate alcohol intake was associated with increased BC risk, particularly for women with ER-positive BC, but only for those at lower predicted familial BC risk (5-year BOADICEA < 1.25). For women with a high FRP (5-year BOADICEA ≥ 6.5%) who also consumed alcohol, being a current smoker was associated with increased BC risk.

中文翻译：

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饮酒，吸烟和家族性乳腺癌风险：前瞻性家庭研究队列（ProF-SC）的发现。

背景技术饮酒和吸烟与罹患乳腺癌（BC）的风险增加相关，但尚不清楚这些关联是否因女性家族性BC风险而异。方法使用前瞻性家庭研究队列，我们​​评估了饮酒，吸烟和BC风险之间的关联。我们使用多变量Cox比例风险模型来估计风险比（HR）和95％置信区间（CI）。我们检查了家族风险谱（FRP）是否修改了关联，家族风险谱（FRP）是通过基于谱系的乳腺癌卵巢疾病发病率分析和携带者估计算法（BOADICEA）预测的BC的1年发病率。结果我们在中位随访时间10.4年中观察到了17435名女性的1009例BC病例。我们发现吸烟或饮酒与BC风险没有总体相关性（目前吸烟者与从未吸烟者相比HR 1.02，95％CI 0.85-1.23;与非常规饮者HR 1.10，95％CI 0.92-相比，每周饮酒≥7次1.32），但我们确实观察到了基于FRP和雌激素受体（ER）状态的关联差异。FRP较低的女性与每周不超过7次饮酒相比，ER阳性BC风险增加（与非常规饮酒者相比），而FRP较高的女性则没有关联。例如，处于FRP第十个百分点（5年BOADICEA = 0.15％）的女性的HR估计为1.46（95％CI 1.07-1.99），而处于90％百分数（5年BOADICEA）的女性则没有关联= 4.2％）（HR 1.07，95％CI 0.80-1.44）。虽然玻璃钢并未改变与吸烟的关系，我们还观察到FRP的正向乘法互动（互动= 0.01）在也饮酒的女性中的吸烟状况，但在非经常饮酒的女性中则没有。结论适度饮酒与增加的BC风险有关，特别是对于ER阳性BC的女性，但仅适用于预测的家族性BC风险较低的妇女（5年BOADICEA <1.25）。对于FRP高的女性（5年BOADICEA≥6.5％）并且也饮酒的女性，目前吸烟者与BC风险增加相关。但仅适用于预测的家族性BC风险较低的患者（5年BOADICEA <1.25）。对于FRP高的女性（5年BOADICEA≥6.5％）并且也饮酒的女性，目前吸烟者与BC风险增加相关。但仅适用于预测的家族性BC风险较低的患者（5年BOADICEA <1.25）。对于FRP高的女性（5年BOADICEA≥6.5％）并且也饮酒的女性，目前吸烟者与BC风险增加相关。