Objectives: Tobacco and alcohol use are established risk factors for esophageal squamous cell carcinoma (ESCC). We sought to determine whether these factors act synergistically to increase the risk of ESCC.
Methods: We performed a systematic literature search in multiple electronic databases regardless of language. Eligible studies were population-based case-control or cohort studies of ESCC that assessed the effects of tobacco and/or alcohol. Departures from multiplicative effects were quantified by the synergy factor (SF); SF >1 indicates positive synergy. Meta-analyses were performed to estimate summary-adjusted odds ratios (ORs) and the summary crude SF using random-effect models. Heterogeneity was defined by Cochrane's Q P<0.10 and the inconsistency index.
Results: Systematic review identified 7,629 unique citations, of which 5 were eligible. Either tobacco or alcohol use was associated with a 20-30% increased risk for ESCC compared with nonuse, but the use of both was associated with an approximately threefold risk for ESCC; the summary-adjusted OR for combined alcohol and tobacco use was 3.28 (95% confidence interval (CI)=2.11, 508; Cochrane's Q P value=0.05; I(2)=55.3%). The summary SF for ever-use of both tobacco and alcohol was 1.85 (95% CI=1.45, 2.38; Cochrane's Q P value=0.49; I(2)=0.0%).
Conclusions: There is a positive synergistic effect of alcohol and tobacco use for ESCC. The observed combined effect of the two factors is almost double if there were no synergy. Efforts for controlling the burden of ESCC should focus on individuals who use both alcohol and tobacco.