PO.PS01.06 · 人群科学
遗传因素与生活方式因素对多族裔队列研究中绝经后浸润性乳腺癌风险的影响
The impact of genetic and lifestyle factors on the risk of invasive postmenopausal breast cancer in the multiethnic cohort study
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：坚持健康生活方式一直与乳腺癌风险降低相关，但这一获益是否因遗传易感性不同而有所差异仍不明确，尤其是在种族和族裔多样化的人群中。本研究评估了在多族裔队列（Multiethnic Cohort, MEC）的绝经后女性中，健康生活方式指数评分（Healthy Lifestyle Index Score, HLIS）与乳腺癌风险之间的关联是否因313个变异位点的多基因风险评分（polygenic risk score, PRS）不同而有所差异。
方法：HLIS（范围：0-7）依据2018年世界癌症研究基金会/美国癌症研究所（World Cancer Research Fund/American Institute for Cancer Research）癌症预防建议构建，包含九项膳食与生活方式成分：水果和蔬菜摄入量、总纤维摄入量、红肉摄入量、饮酒量、体力活动、体质指数（BMI）、腰围（waist circumference, WC）、吸烟状态和含糖饮料摄入量。HLIS依据非病例人群中的分布被分为三分位（低、中、高）。采用以年龄为时间尺度的多变量Cox比例风险模型估计风险比（hazard ratio, HR）及95%置信区间（confidence interval, CI）。简约模型对乳腺癌家族史、受教育程度、绝经类型、产次、每日能量摄入、PRS和前10个主成分（principal component, PC）进行了校正，扩展模型另外对糖尿病史、绝经年龄、初潮年龄和激素使用进行了校正。分析进一步按PRS（高于或低于中位数）进行分层，并使用似然比检验来检验交互作用。
结果：在22,725名绝经后女性中（非西班牙裔白人[22.2%]、非裔美国人[12.9%]、夏威夷原住民[8.1%]、日裔美国人[37.5%]和拉丁裔[19.2%]），在平均12.2年的随访期间有1,174人发生乳腺癌。较高的HLIS与显著较低的乳腺癌风险相关。与处于低HLIS三分位的女性相比，中三分位者的乳腺癌风险降低12%（HR = 0.88；95% CI：0.77-1.00；P = 0.05），高三分位者降低34%（HR = 0.66；95% CI：0.56-0.77；P < 0.001），扩展模型中的结果相似。这一负相关似乎主要由BMI（肥胖 vs. 正常：HR=1.36，95% CI：1.13-1.64，P=0.001）和WC（≥88 cm vs. <80 cm：HR=1.43，95% CI = 1.19-1.72，P < 0.001）驱动。PRS与乳腺癌风险显著相关（每增加1个标准差 HR = 1.37；95% CI：1.29-1.45；P < 0.001）。HLIS与乳腺癌风险之间的负相关在各PRS分层中相似，无显著交互作用（P-int = 0.48）。
结论：在这一由绝经后女性组成的多族裔队列中，无论PRS高低，坚持健康生活方式均与乳腺癌风险降低相关，支持了生活方式调整作为跨越不同人群的乳腺癌关键预防策略的重要性。
查看英文原文 English abstract
Background: Adherence to a healthy lifestyle has been consistently associated with reduced breast cancer risk, but whether this benefit varies by genetic susceptibility remains unclear, particularly among racially and ethnically diverse populations. This study evaluated whether the association between a Healthy Lifestyle Index Score (HLIS) and breast cancer risk differs by a 313-variant polygenic risk score (PRS) among postmenopausal women in the Multiethnic Cohort (MEC).
Methods: HLIS (range: 0-7) was constructed based on the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and included nine dietary and lifestyle components: fruit and vegetable intake, total fiber intake, red meat intake, alcohol consumption, physical activity, body mass index (BMI), waist circumference (WC), smoking status, and sugar-sweetened drink intake. HLIS was categorized into tertiles (low, intermediate, high) according to its distribution among non-cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models with age as the time metric. The parsimonious model was adjusted for family history of breast cancer, educational attainment, type of menopause, parity, daily energy intake, PRS, and the top 10 principal components (PCs), while the extended model was additionally adjusted for history of diabetes, age at menopause, age of menarche, and hormone use. Analyses were further stratified by PRS (above vs. below the median), and interaction was tested using a likelihood ratio test.
Results: Among the 22,725 postmenopausal women (non-Hispanic White [22.2%], African American [12.9%], Native Hawaiian [8.1%], Japanese American [37.5%], and Latino [19.2%]), 1,174 developed breast cancer during an average follow-up of 12.2 years. Higher HLIS was associated with a significantly lower risk of breast cancer. Compared to women in the low HLIS tertile, breast cancer risk was 12% lower (HR = 0.88; 95% CI: 0.77-1.00; P = 0.05) in the intermediate tertile and 34% lower (HR = 0.66; 95% CI: 0.56-0.77; P < 0.001) in the high tertile, with similar results in the extended model. This inverse association appeared to be driven by BMI (obese vs. normal: HR=1.36, 95% CI: 1.13-1.64, P=0.001) and WC (≥88 cm vs. <80 cm: HR=1.43, 95% CI = 1.19-1.72, P < 0.001). PRS was significantly associated with breast cancer risk (per-SD HR = 1.37; 95% CI: 1.29-1.45; P < 0.001). The inverse association between HLIS and breast cancer risk was similar across PRS strata, with no significant interaction (P-int = 0.48).
Conclusion: In this multiethnic cohort of postmenopausal women, adherence to a healthy lifestyle was associated with a reduced risk of breast cancer, regardless of low or high PRS, supporting the importance of lifestyle modification as a key preventive strategy for breast cancer across diverse populations.
利益披露 Disclosure
C. Zhao, None..
G. Maskarinec, None..
D. Conti, None..
C. A. Haiman, None..
L. R. Wilkens, None..
F. Chen, None..
E. Lee, None.