The Combined Effects of Alcohol Consumption and Smoking on Cancer Risk by Exposure Level: A Systematic Review and Meta-Analysis

Background: Alcohol consumption is a major risk factor for cancer, and when combined with smoking, the risk increases. Nevertheless, few studies have comprehensively evaluated the combined effects of alcohol consumption and smoking on the risk of various cancer types. Therefore, to assess these effects, we conducted a systematic review and meta-analysis. Methods: We performed a systematic search of five literature databases, focusing on cohort and case-control studies. Considering exposure levels, we quantified the combined effects of alcohol consumption and smoking on cancer risk and assessed multiplicative interaction effects. Results: Of 4,452 studies identified, 24 (4 cohort studies and 20 case-control studies) were included in the meta-analysis. We detected interaction effect of light alcohol and moderate smoking on head and neck cancer risk (relative risk [RR], 4.26; 95% confidence interval [CI], 2.50–7.26; I2 = 65%). A synergistic interaction was observed in heavy alcohol and heavy smoking group (RR, 35.24; 95% CI, 23.17–53.58; I2 = 69%). In more detailed cancer types, the interaction effect of heavy alcohol and heavy smoking was noticeable on oral (RR, 36.42; 95% CI, 24.62–53.87; I2 = 46%) and laryngeal (RR, 38.75; 95% CI, 19.25–78.01; I2 = 69%) cancer risk. Conclusion: Our study provided a comprehensive summary of the combined effects of alcohol consumption and smoking on cancers. As their consumption increased, the synergy effect became more pronounced, and the synergy effect was evident especially for head and neck cancer. These findings provide additional evidence for the combined effect of alcohol and smoking in alcohol guidelines for cancer prevention.