Endogenous antioxidant biomarkers and cancer risk among men with concurrent smoking and alcohol use: A prospective cohort study

Abstract

Background: This study aimed to evaluate age-specific associations between endogenous antioxidant biomarkers and cancer risk in a high-risk male population characterized by concurrent smoking and alcohol use. Methods: We analyzed data from the Korean Cancer Prevention Study-II (KCPS-II), including 83,371 men. Associations between serum creatinine, bilirubin, albumin, and uric acid and cancer risk were evaluated using Cox proportional hazards models. Analyses were conducted among all men, ever smokers and drinkers, and current smokers and drinkers, with both overall and age-stratified analyses (<50 and ≥50 years). Restricted cubic spline analyses were performed to assess nonlinear age-dependent associations and age–biomarker interactions. Results: Serum bilirubin, albumin, and uric acid were inversely associated with overall cancer risk, with the strongest associations observed among men aged ≥ 50 years with concurrent smoking and alcohol use. Creatinine demonstrated contrasting associations according to age. Lung cancer showed consistent inverse associations across biomarkers, whereas stomach, prostate, and pancreatic cancers exhibited heterogeneous age-specific patterns. Restricted cubic spline analyses further indicated significant nonlinear age–biomarker interactions. Conclusions: Among men with concurrent smoking and alcohol use, biomarker–cancer associations showed substantial age-dependent heterogeneity in both magnitude and direction. © 2026 Elsevier Ltd