Methylation-Based Biological Age and Breast Cancer Risk
Methylation-Based Biological Age and Breast Cancer Risk
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DOI：
10.1093/jnci/djz020
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发表时间：
2019-10-01
影响因子：
10.3
通讯作者：
Taylor, Jack A.
中科院分区：
文献类型：
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作者：
Kresovich, Jacob K.;Xu, Zongli;Taylor, Jack A.
年龄是癌症、慢性病和死亡率的最强预测因子之一，但不同的人对衰老的生物反应不同。表观遗传DNA修饰已被用于估计“生物年龄”，这可能是一个有用的疾病风险预测。我们测试了这一假设为breastcancer.Methods使用的情况下，队列的方法，我们测量了基线血液DNA甲基化的2764名妇女参加了姐妹研究，其中1566人随后发展为乳腺癌后，平均6年。使用三个先前建立的基于甲基化的“时钟”（Hannum，Horvath和Levine），我们通过比较每个女性的估计生物年龄与实际年龄来定义生物年龄加速。使用考克斯回归模型估计乳腺癌风险的风险比和95%置信区间。所有统计检验都是双侧的。结果三个时钟中的每一个都表明，生物年龄加速与患乳腺癌的风险增加在统计学上显着相关（5岁年龄加速，汉纳姆时钟：风险比[HR] = 1.10，95%置信区间[CI] = 1.00至1.21，P= 0.04;霍瓦特时钟：HR = 1.08，95% CI = 1.00 - 1.17，P= 0.04; Levine时钟：HR = 1.15，95% CI = 1.07 - 1.23，P
Background Age is one of the strongest predictors of cancer, chronic disease, and mortality, but biological responses to aging differ among people. Epigenetic DNA modifications have been used to estimate "biological age," which may be a useful predictor of disease risk. We tested this hypothesis for breast cancer.Methods Using a case-cohort approach, we measured baseline blood DNA methylation of 2764 women enrolled in the Sister Study, 1566 of whom subsequently developed breast cancer after an average of 6 years. Using three previously established methylation-based "clocks" (Hannum, Horvath, and Levine), we defined biological age acceleration for each woman by comparing her estimated biological age with her chronological age. Hazard ratios and 95% confidence intervals for breast cancer risk were estimated using Cox regression models. All statistical tests were two-sided.Results Each of the three clocks showed that biological age acceleration was statistically significantly associated with increased risk of developing breast cancer (5-year age acceleration, Hannum's clock: hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.00 to 1.21, P=.04; Horvath's clock: HR = 1.08, 95% CI = 1.00 to 1.17, P=.04; Levine's clock: HR = 1.15, 95% CI = 1.07 to 1.23, P