Attributable fraction and interaction of tobacco smoking and alcohol drinking on the risk of head and neck cancer: a pooled analysis of 11 prospective cohort studies in Japan

BACKGROUND: Tobacco smoking and alcohol drinking are major risk factors for head and neck cancer (HNC), but their interaction effects have not been investigated in the Japanese population. METHODS: We conducted a pooled analysis using data from 11 prospective cohorts in Japan, covering a total of 434 431 participants with 5 969 082 person-years of follow-up. Cox proportional hazards model analyses were performed separately in each cohort. Interactions and population-attributable fractions (PAFs) were estimated through meta-analyses. RESULTS: During follow-up, 1835 incidents of HNC were newly identified. Both smoking and drinking habits significantly increased HNC risk. Subsite analysis showed that smoking increased risk in several subsites, while drinking was associated with hypopharyngeal cancer only. The multiplicative interaction was 1.55 [95% confidence interval (CI): 1.12-2.14] and the additive interaction (relative excess risk due to interaction) was 0.87 (95% CI: 0.42-1.36). Among men, PAFs were 0.414 for smoking and 0.336 for drinking, while the combined PAF was 0.469. Subsite-specific analysis showed larger PAFs of smoking in the nasopharynx and larynx, and larger PAFs of drinking in the oral cavity and hypopharynx. CONCLUSION: Tobacco smoking and alcohol drinking interact to increase the risk of HNC in the Japanese population. The attributable fraction of each factor differs by subsite. These findings may aid the development of future preventive strategies for HNC.