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

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.