Individual and social contextual factors in relation to DNA methylation, biological aging, and lung cancer risk

Lung cancer is the leading cause of cancer death in both men and women. African Americans (AAs)
have a higher risk of lung cancer than European Americans (EAs) and any other racial group in the U.S. In
addition, socioeconomically disadvantaged populations suffer a higher burden of lung cancer than more
We recently found that AA males living in deprived neighborhoods had up to a 1.5-fold
increased risk of lung cancer than those living in better neighborhoods. We also found that healthy eating was
associated with a lower risk of lung cancer. However, the biological mechanisms linking the
DNA methylation, one of the most frequent and important epigenetic
modifications, plays a crucial role in regulating gene expression and cell function. Lifestyle and socioeconomic
status (SES) factors may affect health through methylation modifications AAs and
affluent populations.
socioeconomic
factors with lung cancer is not clear.
. In addition, SES
disadvantaged populations endure a greater acceleration of biological aging. However, how the
individual and
social SES and lifestyle factors
affect DNA methylation, biological aging, and lung cancer risk in AAs and
socioeconomically disadvantaged populations is largely unknown. The ongoing NCI-funded Southern
Community Cohort Study (SCCS), a landmark investigation tracking a cohort of ~86,000 adults, two-thirds AAs
and one-third non-Hispanic EAs, shows a similar low SES among AAs and EAs. Building on these unique
resources, we will conduct the first well-powered prospective social epigenomics study in a cohort at an
elevated lung cancer risk. We will perform genome-wide methylation assays for pre-diagnostic blood samples
from 1,250 incident lung cancer cases (800 AAs and 450 EAs) and 1,700 individually-matched controls (800
AAs and 900 EAs). Using these methylation data, along with rich epidemiological data collected in the SCCS,
we will: identify methylation markers and patterns in association with race (self-reported and genetically
determined), individual and
social
SES, and lifestyle factors (Aim 1) and further investigate whether DNA
methylation markers and patterns identified in Aim 1 are associated with lung cancer risk (Aim 2); investigate
the associations between lifestyle and SES factors with biological aging (methylation-based age and age
acceleration) (Aim 3) and investigate whether biological aging is associated with lung cancer risk (Aim 4). We
will further investigate the potential effect of SES and lifestyle factor changes on DNA methylation and
biological aging. We will also conduct in vitro functional investigation of promising methylation sites and their
regulated genes. Because detailed epidemiological data and biological samples have already been collected in
the parent study, this proposed project is both highly feasible and extremely cost-efficient. Findings from this
study may provide insights into how
individual and social contextual factors
affect DNA methylation and help us
to better understand the mechanistic relationships between SES/lifestyle factors and lung cancer risk. The
findings may also provide useful information which could be used to ameliorate the lung cancer disparities.

Grant Number: 5R01MD015396-05
NIH Institute/Center: NIH
Principal Investigator: QIUYIN CAI