Epigenetic assessments of alcohol consumption predict mortality in smokers at risk for lung cancer in the prostate, lung, colorectal and ovarian cancer screening trial

Robert Philibert; Steven R H Beach; James A Mills; Kelsey Dawes; Richard M Hoffman; Jessica C Sieren; Ellyse M Froehlich; Kaitlyn M deBlois; Jeffrey D Long

doi:10.1371/journal.pone.0322783

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Epigenetic assessments of alcohol consumption predict mortality in smokers at risk for lung cancer in the prostate, lung, colorectal and ovarian cancer screening trial

Journal article

Open access

Peer reviewed

Epigenetic assessments of alcohol consumption predict mortality in smokers at risk for lung cancer in the prostate, lung, colorectal and ovarian cancer screening trial

Robert Philibert, Steven R H Beach, James A Mills, Kelsey Dawes, Richard M Hoffman, Jessica C Sieren, Ellyse M Froehlich, Kaitlyn M deBlois and Jeffrey D Long

PloS one, Vol.20(5), e0322783

05/22/2025

DOI: 10.1371/journal.pone.0322783

PMCID: PMC12097613

PMID: 40402951

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Abstract

DNA methylation at cg05575921, an established biomarker for smoking predicts risk for lung cancer (LC). Although heavy alcohol consumption (HAC) frequently accompanies smoking, the relationship of HAC to overall mortality in those at risk for LC is not well known. Determining the contribution of HAC to mortality in those who smoke is important because HAC is also a major driver of mortality and is potentially treatable. To help answer this question, we examined the relationship of epigenetic biomarkers of smoking (cg05575921) and chronic heavy alcohol consumption (Alcohol T Score, ATS) in a cohort of 92 LC cases and 402 age, sex, ethnicity and smoking history matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial to all-cause mortality using proportional hazards survival analysis. We found that ATS values significantly predicted risk for all-cause mortality in those smokers who developed (p < 0.03) and did not develop lung cancer (p < 0.0001). When mortality data were analyzed using median splits, those who did and did not incur lung cancer with ATS values <3.6 lived 5.6 years and 3.2 years more, respectfully, than those with ATS values >3.6. Interestingly, in this group of 494 smokers or former smokers, after adjusting for the occurrence of lung cancer, cg05575921 methylation did not predict mortality. In summary, we found that excessive alcohol consumption is a significant risk factor for all-cause mortality in those at risk for LC and suggest that lung cancer screening efforts to address problem drinking could increase survival.

Aged

Alcohol Drinking - adverse effects

Alcohol Drinking - genetics

Alcohol Drinking - mortality

Colorectal Neoplasms - genetics

DNA Methylation

Early Detection of Cancer

Epigenesis, Genetic

Female

Humans

Lung Neoplasms - diagnosis

Lung Neoplasms - genetics

Lung Neoplasms - mortality

Male

Middle Aged

Ovarian Neoplasms - genetics

Ovarian Neoplasms - mortality

Prostatic Neoplasms - genetics

Risk Factors

Smokers

Smoking - adverse effects

Smoking - genetics

Smoking - mortality

Details

Title: Subtitle: Epigenetic assessments of alcohol consumption predict mortality in smokers at risk for lung cancer in the prostate, lung, colorectal and ovarian cancer screening trial
Creators: Robert Philibert - University of Iowa
Steven R H Beach - University of Georgia
James A Mills - University of Iowa
Kelsey Dawes - Behavioral Diagnostics
Richard M Hoffman - University of Iowa
Jessica C Sieren - University of Iowa
Ellyse M Froehlich - University of Iowa
Kaitlyn M deBlois - University of Iowa
Jeffrey D Long - University of Iowa
Resource Type: Journal article
Publication Details: PloS one, Vol.20(5), e0322783
DOI: 10.1371/journal.pone.0322783
PMID: 40402951
PMCID: PMC12097613
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: PUBLIC LIBRARY SCIENCE
Grant note: National Institutes of Health: 1R44CA285136
National Institutes of Health 1R44CA285136.
Language: English
Date published: 05/22/2025
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Iowa Neuroscience Institute; Biostatistics; General Internal Medicine; Internal Medicine
Record Identifier: 9984824331402771

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