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The Synergistic Effects of Alcohol and Tobacco Consumption on the Risk of Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Prabhu, Anoop MD1; Obi, Kenneth O MD2; Rubenstein, Joel H MD, MSc1

American Journal of Gastroenterology: June 2014 - Volume 109 - Issue 6 - p 822–827
doi: 10.1038/ajg.2014.71

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 QP<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 QPvalue=0.05;I2=55.3%). The summary SF for ever-use of both tobacco and alcohol was 1.85 (95% CI=1.45, 2.38; Cochrane's QPvalue=0.49;I2=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.

1 VA Medical Center, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA

2 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA

Correspondence: Joel H. Rubenstein, MD, MSc, VA Medical Center, Division of Gastroenterology, University of Michigan Medical School, 111-D, 2215 Fuller Road, Ann Arbor, Michigan 48105, USA. E-mail:

Received 2 October 2013; accepted 2 March 2014

published online 15 April 2014

© The American College of Gastroenterology 2014. All Rights Reserved.
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