Epigenetic mortality predictors and incidence of breast cancer
Epigenetic mortality predictors and incidence of breast cancer
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DOI：
10.18632/aging.102523
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发表时间：
2019-12-31
期刊：
影响因子：
5.2
通讯作者：
Taylor, Jack A.
中科院分区：
文献类型：
--
作者：
Kresovich, Jacob K.;Xu, Zongli;Taylor, Jack A.
使用血液DNA甲基化的措施越来越多地作为疾病和死亡风险的指标进行调查。三种现有的表观遗传年龄测量或“表观遗传时钟”似乎与乳腺癌有关。两个新开发的表观遗传死亡率预测因子可能与所有癌症发病率相关，但与特定癌症的关联尚未在大型研究中进行研究。使用HumanMethylation 450 BeadChips测量参加姐妹研究的2，773名无癌症妇女的血液DNA甲基化，我们计算了两个表观遗传死亡率预测因子：“GrimptenoAccel”和“死亡率评分”（MS）。使用考克斯比例风险模型，Grimendo Accel和MS均与总体乳腺癌发病率无关（Grimendo加速风险比[HR]：1.06，95%置信区间[CI]：0.98-1.14，P=0.17; MS HR：0.99，95% CI：0.92-1.07，P=0.85）;然而，观察到Grimendix Accel与浸润性乳腺癌之间存在弱的正相关性（HR：1.08，95% CI：0.99-1.17，P=0.08）。根据诊断时的绝经状态对浸润性癌症进行分层，发现主要在绝经后乳腺癌中观察到相关性（HR：1.10，95% CI：1.01，1.20，P=0.04）。虽然MS与乳腺癌风险无关，但我们发现有证据表明Grimesium Accel可能与浸润性乳腺癌相关性较弱，特别是对于绝经后诊断的女性。
Measures derived using blood DNA methylation are increasingly under investigation as indicators of disease and mortality risk. Three existing epigenetic age measures or "epigenetic clocks" appear associated with breast cancer. Two newly-developed epigenetic mortality predictors may be related to all-cancer incidence, but associations with specific cancers have not been examined in large studies. Using HumanMethylation450 BeadChips to measure blood DNA methylation in 2,773 cancer-free women enrolled in the Sister Study, we calculated two epigenetic mortality predictors: 'GrimAgeAccel' and the 'mortality score' (MS). Using Cox proportional hazard models, neither GrimAgeAccel nor the MS were associated with overall breast cancer incidence (GrimAgeAccel hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 0.98-1.14, P=0.17; MS HR: 0.99, 95% CI: 0.92-1.07, P=0.85); however, a weak, positive association was observed for GrimAgeAccel and invasive breast cancer (HR: 1.08, 95% CI: 0.99-1.17, P=0.08). Stratification of invasive cancers by menopause status at diagnoses revealed the association was predominantly observed for postmenopausal breast cancer (HR: 1.10, 95% CI: 1.01, 1.20, P=0.04). Although the MS was unrelated to breast cancer risk, we find evidence that GrimAgeAccel may be weakly associated with invasive breast cancer, particularly for women diagnosed after menopause.