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

Morgan E Levine,H Dean Hosgood,Brian Chen,Steve Horvath,Themistocles Assimes,Devin Absher

doi:10.18632/aging.100809

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.

Highlights

Lung cancer is one of the most deadly of all cancers
We have developed a highly accurate candidate biomarker of aging based on DNA methylation (DNAm) levels [10], known as the “epigenetic clock”, which can be used to measure the age of human cells, tissues, and organs
We examined whether intrinsic epigenetic age acceleration (IEAA)— which refers to epigenetic age acceleration adjusted for abundance measures of blood cell counts—predicts development of lung cancer

Summary

Introduction

Lung cancer is one of the most deadly of all cancers. While lung cancer accounts for only 14% of cancer incidence, it has an overall 5-year survival rate below 20% [1] and contributes to over a quarter of all cancer deaths [2]. In 2012 alone, an estimated 1.6 million people worldwide died from lung cancer. Lung cancer carries a high financial burden, costing the United States about $12 billion, annually [3] and as a result, prevention of lung cancer has become a key area of focus in medical research. Decades of research has identified smoking as the leading preventable cause of lung cancer, for which it is estimated to contribute to nearly 90% of all cases [4]. Lung cancer was an exceedingly rare disease at the end of the 19th century

Methods

Results

Conclusion