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

Morgan E. Levine, Howard D. Hosgood, Brian Chen, Devin Absher, Themistocles Assimes, Steve Horvath

Research output: Contribution to journalArticle

81 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)690-700
Number of pages11
JournalAging
Volume7
Issue number9
StatePublished - 2015

Fingerprint

Women's Health
DNA Methylation
Lung Neoplasms
Epigenomics
Biomarkers
Genomic Instability
Incidence
Proportional Hazards Models
Individuality
Smoke
Tobacco Products
Carcinogens
Disease Progression

Keywords

  • Biological age
  • Epigenetic clock
  • Lung cancer

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Levine, M. E., Hosgood, H. D., Chen, B., Absher, D., Assimes, T., & Horvath, S. (2015). DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative. Aging, 7(9), 690-700.

DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative. / Levine, Morgan E.; Hosgood, Howard D.; Chen, Brian; Absher, Devin; Assimes, Themistocles; Horvath, Steve.

In: Aging, Vol. 7, No. 9, 2015, p. 690-700.

Research output: Contribution to journalArticle

Levine, ME, Hosgood, HD, Chen, B, Absher, D, Assimes, T & Horvath, S 2015, 'DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative', Aging, vol. 7, no. 9, pp. 690-700.
Levine, Morgan E. ; Hosgood, Howard D. ; Chen, Brian ; Absher, Devin ; Assimes, Themistocles ; Horvath, Steve. / DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative. In: Aging. 2015 ; Vol. 7, No. 9. pp. 690-700.
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