Sex-specific associations of creatinine and antioxidant biomarkers with lung cancer risk by drinking and smoking behavior: A prospective cohort study

Abstract

Background: This study aimed to evaluate the associations between serum creatinine, a potential antioxidant marker, and major endogenous antioxidant biomarkers with lung cancer risk, stratified by sex, alcohol consumption, and smoking status. Methods: We analyzed 133,596 cancer-free adults from the Korean Cancer Prevention Study II (KCPS-II) cohort. During a mean follow-up of 13.5 years, 721 incident lung cancer cases were identified. Serum levels of creatinine, total bilirubin, albumin, and uric acid were measured. Alcohol consumption and smoking status were classified as never, former, current, and ever users, with ever users including both current and former users. Individuals with both alcohol and smoking exposure were additionally analyzed as a high-risk group. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for lung cancer, stratified by alcohol and smoking status. Biomarkers were analyzed by quartiles and linear trends. Results: A 1-SD increase in serum creatinine was inversely associated with lung cancer risk in the overall population, including current drinkers (HR: 0.85, 95 % CI: 0.73-0.98), ever drinkers (HR: 0.85, 95 % CI: 0.75-0.97), former smokers (HR: 0.77, 95 % CI: 0.62-0.96), and ever smokers (HR: 0.81, 95 % CI: 0.70-0.93). In men, similar associations were observed in current drinkers (HR: 0.83, 95 % CI: 0.72-0.97), ever drinkers (HR: 0.86, 95 % CI: 0.75-0.99), former smokers (HR: 0.77, 95 % CI: 0.62-0.96), and ever smokers (HR: 0.80, 95 % CI: 0.70-0.92). High-risk groups exposed to both smoking and alcohol showed consistent inverse associations, with current smokers who were also current drinkers (HR: 0.81, 95 % CI: 0.66-1.00), and ever smokers who were also ever drinkers (HR: 0.78, 95 % CI: 0.67-0.91). No significant association was observed in women. Conclusions: In men, serum creatinine showed a strong inverse association with lung cancer risk under oxidative stress conditions related to smoking and alcohol consumption.