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Research Paper|Volume 7, Issue 9|pp 690—700

DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative

Morgan E. Levine1,2, H. Dean Hosgood3, Brian Chen4, Devin Absher5, Themistocles Assimes6, Steve Horvath1,7
  • 1Human Genetics, David Geffen School of Medicine, University of California LA, Los Angeles, CA 90095, USA
  • 2Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA
  • 3Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
  • 4Longitudinal Study Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
  • 5HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA
  • 6Department of Medicine, Stanford University School of Medicine, Stanford, CA Stanford University School of Medicine, Stanford, CA 94305, USA
  • 7Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
* Joint senior authors
Received: August 19, 2015Accepted: September 12, 2015Published: September 24, 2015
https://doi.org/10.18632/aging.100809

Copyright: © 2015 Levine et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Lung cancer is considered an age-associated disease, whose progression is in part due to accumulation of genomic instability as well as age-related decline in system integrity and function. Thus even among individuals exposed to high levels of genotoxic carcinogens, such as those found in cigarette smoke, lung cancer susceptibility may vary as a function of individual differences in the rate of biological aging. We recently developed a highly accurate candidate biomarker of aging based on DNA methylation (DNAm) levels, which may prove useful in assessing risk of aging-related diseases, such as lung cancer. Using data on 2,029 females from the Women's Health Initiative, we examined whether baseline measures of “intrinsic epigenetic age acceleration” (IEAA) predicted subsequent lung cancer incidence. We observed 43 lung cancer cases over the nearly twenty years of follow-up. Results showed that standardized measures of IEAA were significantly associated with lung cancer incidence (HR: 1.50, P = 3.4×10−3). Furthermore, stratified Cox proportional hazard models suggested that the association may be even stronger among older individuals (70 years or above) or those who are current smokers. Overall, our results suggest that IEAA may be a useful biomarker for evaluating lung cancer susceptibility from a biological aging perspective.