Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
Int J Cancer. 2018 Apr 15;142(8):1611-1619. doi: 10.1002/ijc.31189. Epub 2017 Dec 18.
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.
衰老和癌症之间的关系很复杂。最近的研究基于 DNA 甲基化开发了衡量生物衰老的指标，并将其称为“年龄加速”。我们旨在评估年龄加速与七种常见癌症的发病风险和生存之间的关联。这项研究纳入了墨尔本合作队列研究中的 7 项基于 DNA 甲基化的结肠癌、胃癌、肾癌、肺癌、前列腺癌和膀胱癌以及 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链接确定癌症病例、生存状态和死亡原因。使用条件逻辑回归和 Cox 模型来估计与 5 种源自 Human Methylation 450 K Beadchip 检测的年龄加速指标相关的癌症发病风险（n=3216 例病例）和生存（n=1726 例死亡）的比值比（OR）和风险比（HR）及其 95%置信区间（CI）。表观遗传衰老与癌症风险增加相关，在考虑的 5 个指标中，每增加五年的年龄加速，癌症风险增加 4%至 9%。观察到研究间存在异质性，在肾癌和 B 细胞淋巴瘤的发病风险中观察到更强的关联。在癌症诊断后，死亡率每增加五年的年龄加速，风险增加 2%至 6%，但没有观察到癌症部位的异质性。与年龄加速的第一四分位数相比，第四四分位数的癌症风险和死亡率增加了 15%至 30%。基于 DNA 甲基化的生物衰老衡量指标与癌症风险增加和癌症生存时间缩短独立相关，与主要健康风险因素无关。
