Alcohol, Alcoholic Beverages and Risk of Esophageal Cancer by Histological Type: A Dose-Response Meta-Analysis of Observational Studies

Aims: We conducted a dose-response meta-analysis to explore the association between alcohol and particular alcoholic beverages with risk of esophageal cancer (EC) by histological type [esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC)] and whether the association differs according to gender. Methods: PubMed and Web of Science databases were searched for relevant articles published between January 1960 and December 2019. The pooled relative ratios (RRs) and 95% confidence interval (CI) were calculated with the fixed or random effect model. The dose-response relationship was assessed by restricted cubic spline. Results: A total of 74 published articles involving 31,105 cases among 3,369,024 participants were included in this meta-analysis. The pooled RRs of the highest versus lowest alcohol intake were 3.67 (95% CI, 2.89,4.67) for EC, 5.11 (95% CI, 3.60,7.25) for ESCC and 0.96 (95% CI, 0.79,1.16) for EAC. The above-mentioned associations were observed in cohort design, for different alcoholic beverages (beer, wine and liquor/spirits) and gender. Evidence of a nonlinear dose-response relationship for EC risk with alcohol intakewas found (Pnon-linearity < 0.001), and a linear relationship (Pnon-linearity = 0.216) suggested that the risk of ESCC increased by 33% for every 12.5 g/day increment of alcohol intake. Conclusions: This meta-analysis suggests that alcohol intake might significantly increase the incidence of EC, especially for ESCC.