DNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies
DNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies
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基于DNA甲基化的生物衰老与癌症风险和生存率：7项前瞻性研究的汇总分析
DOI：
10.1002/ijc.31189
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发表时间：
2018-04-15
影响因子：
6.4
通讯作者：
Milne, Roger L.
中科院分区：
文献类型：
--
作者：
Dugue, Pierre-Antoine;Bassett, Julie K.;Milne, Roger L.
衰老和癌症之间的关系是复杂的。最近的研究开发了基于DNA甲基化的生物衰老措施，并将其称为“年龄加速”。“我们的目的是评估年龄加速与七种常见癌症的风险和生存率的关系。在墨尔本协作队列研究中进行了7项DNA甲基化与结直肠癌、胃癌、肾癌、肺癌、前列腺癌和尿路上皮癌以及B细胞淋巴瘤的病例对照研究。通过与癌症和死亡登记处的联系，确定了癌症病例、生命状态和死亡原因。使用条件logistic回归和考克斯模型分别估计来自人类甲基化450 K Beadchip检测的5种年龄加速指标与癌症风险（N = 3，216例）和生存率（N = 1，726例死亡）相关性的比值比（OR）和风险比（HR）以及95%置信区间（CI）。表观遗传衰老与癌症风险增加有关，对于所考虑的5项措施，每5岁加速4%至9%。通过研究观察到异质性，与肾癌和B细胞淋巴瘤的风险有更强的关联。癌症诊断后死亡的相关风险增加范围为每5岁加速2%至6%，没有证据表明癌症部位的异质性。年龄加速的第四个四分位数与第一个四分位数相比，癌症风险和死亡率增加了15-30%。基于DNA甲基化的生物衰老指标与癌症风险增加和癌症生存期缩短相关，与主要健康风险因素无关。
The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them "age acceleration." We aimed to assess the associations of age acceleration with risk of and survival from seven common cancers. Seven case-control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer and B-cell lymphoma nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450 K Beadchip assay with cancer risk (N = 3,216 cases) and survival (N = 1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five-year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B-cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five-year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15-30% for the fourth versus first quartile of age acceleration. DNA methylation-based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors.