# Genetic and epigenetic risk markers for lung cancer in former smokers

> **NIH NIH P01** · UNIVERSITY OF MINNESOTA · 2022 · $479,506

## Abstract

ABSTRACT
While smoking cessation efforts have resulted in a decrease in smoking and lung cancer rates, lung cancer
remains the second most common cancer and the leading cause of cancer-related deaths for both men and
women. Currently, at least half of the newly incident lung cancer cases are former smokers in the US. Moreover,
there are racial/ethnic differences in smoking-related lung cancer risk; however, it is unclear of the extent these
differences persist after smoking cessation. Low-dose CT screening for lung cancer has been shown to reduce
lung cancer mortality by ~20%; however, screening recommendations are limited to current smokers and recent
quitters (within 15 years) who were moderate or heavy smokers (≥20 pack-year smoking history), which does
not address risk among those who have quit >15 years and/or who are light smokers. Prior genetic, epigenetic,
and molecular marker studies have shown that differences in the frequencies or levels of these markers, may
help to better understand risk differences across populations. Our data suggests that smoking may differentially
influence DNA methylation levels across populations and that genetic, epigenetic, and biochemical markers of
smoking may be associated with lung cancer risk in a multiethnic population independent of self-reported
smoking data. The objective of this proposal is to improve the understanding of the mechanisms of lung cancer
risk in a former smoker population. We propose to evaluate the impact of smoking cessation on lung cancer risk
across five racial/ethnic groups from the Multiethnic Cohort study (MEC) with disparate risk of disease (Aim 1).
We will conduct an epigenome-wide association study (EWAS) of years quit among former smokers from the
MEC (Aim 2). Lastly, we will systematically investigate the association of genetic variants and DNA methylation
from blood leukocytes and urinary cadmium levels (Aim 3) with risk of lung cancer. Additionally, we will interact
with the other three projects in this P01 to study the influence of CYP2A6 genetic variants in relation to years
quit (Project 2), the association of genetic variants with markers of the exposome (Project 3) and the association
for urinary phenanthrene metabolite ratio with DNA methylation of AHRR (Project 4). We hypothesize that
ethnic/racial and individual differences in lung cancer risk in former smokers are in part due to variations in
genetics and different biological response to smoking cessation. The findings from this study will expand our
understanding of risk and potential mechanisms for lung cancer in a multiethnic population of former smokers.
This will help to identify for screening those individuals remaining at greatest risk of lung cancer despite them
having taken the major step of quitting smoking to reduce their risk.

## Key facts

- **NIH application ID:** 10411513
- **Project number:** 2P01CA138338-11
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Sungshim Lani Park
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $479,506
- **Award type:** 2
- **Project period:** 2009-12-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411513

## Citation

> US National Institutes of Health, RePORTER application 10411513, Genetic and epigenetic risk markers for lung cancer in former smokers (2P01CA138338-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10411513. Licensed CC0.

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