title: DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative.
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=3.4x10-3). 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.
authors.affiliation: Human Genetics, David Geffen School of Medicine, University of California LA, Los Angeles, CA 90095, USA.|Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Levine
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.affiliation: Longitudinal Study Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Chen
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Themistocles
authors.initials: T
authors.lastname: Assimes
authors.affiliation: Human Genetics, David Geffen School of Medicine, University of California LA, Los Angeles, CA 90095, USA.|Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood; D015331:Cohort Studies; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D004198:Disease Susceptibility; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis; D016387:Women's Health
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA
keywords: biological age; epigenetic clock; lung cancer