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Int J Cancer. 2018 Apr 15;142(8):1611-1619. doi: 10.1002/ijc.31189. Epub 2017 Dec 18.

DNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies.

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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.
Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
Melbourne Bioinformatics, The University of Melbourne, Parkville, Victoria, Australia.
Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Centre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Université Paris-Saclay, UPS, USQ, Gustave Roussy, Villejuif, France.
Human Genetics Foundation (HuGeF), Turin, Italy.
Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
Genetic Medicine and Familial Cancer Centre, Royal Melbourne Hospital, Parkville, Victoria, Australia.


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.


DNA methylation; age acceleration; aging; biological age; blood; epigenetic aging; epigenetic clock; lymphoma; prospective study; survival

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