Gastroenterology

Gastroenterology

Volume 142, Issue 3, March 2012, Pages 442-452.e5
Gastroenterology

Original Research
Clinical—Alimentary Tract
Nonsteroidal Anti-inflammatory Drug Use Reduces Risk of Adenocarcinomas of the Esophagus and Esophagogastric Junction in a Pooled Analysis

https://doi.org/10.1053/j.gastro.2011.11.019Get rights and content

Background & Aims

Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported to reduce risks of esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations.

Methods

We performed a pooled analysis of 6 population-based studies within the Barrett's and Esophageal Adenocarcinoma Consortium to evaluate the association between NSAID use and the risk of EAC and EGJA, using uniform exposure definitions. We collected information from 6 studies (5 case-control and 1 cohort), with a total of 1226 EAC and 1140 EGJA cases, on aspirin and/or NSAID use. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate adjusted logistic regression models and then pooled using a random effects meta-analysis model.

Results

Compared with nonusers, individuals who have used NSAIDs had a statistically significant reduced risk of EAC (OR, 0.68; 95% CI, 0.56–0.83); they also appeared to have a reduced risk of EGJA (OR, 0.83; 95% CI, 0.66–1.03). Similar reductions in risk were observed among individuals who took aspirin or nonaspirin NSAIDs. The highest levels of frequency (daily or more frequently) and duration (≥10 years) of NSAID use were associated with an approximately 40% reduction in risk of EAC, with ORs of 0.56 (95% CI, 0.43–0.73; Ptrend < .001) and 0.63 (95% CI, 0.45–0.90; Ptrend = .04), respectively.

Conclusions

Although reverse causation could, in part, explain the inverse association observed between NSAID use and EAC risk, our pooled analysis suggests a possible role for NSAIDs in prevention of adenocarcinomas of the esophagus and esophagogastric junction.

Section snippets

Study Populations

Among the 12 BEACON studies, we identified 6 with sufficient information on aspirin and nonaspirin NSAID use to contribute to the pooled analyses of EAC (Table 1). Five studies were population-based case-control studies (the Australian Study of Esophageal Cancer,33 the Nova Scotia Barrett Esophagus Study,34 the US Multicenter Study,24 the Factors Influencing the Barrett's Adenocarcinoma Relationship Study,20 and the Los Angeles County Multi-ethnic Study35) and one was a cohort study (the

Results

The included studies are described in Table 1. The mean age of EAC cases, EGJA cases, and controls was 63.7, 63.1, and 61.7 years, respectively. A large majority of cases (EAC, 88.4%; EGJA, 85.8%) and controls (68.1%) were male. The overall prevalence of ever NSAID use among controls was 69%, which varied between studies from 37% to 87%. Overall, the proportion of persons reporting ever using NSAIDs was 56.6% among EAC cases and 59.6% among EGJA cases compared with 68.6% among controls.

Discussion

We found that users of NSAIDs, in particular those reporting current use, experienced a statistically significant lower risk of EAC than those who did not use these medications. We also observed statistically significant inverse associations between greater frequency and duration of NSAID use and risk of EAC. When the analysis was examined by type of NSAID, the magnitude of the effect for ever use of aspirin was similar to the effect for ever use of nonaspirin NSAIDs. However, there was little

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    This article has an accompanying continuing medical education activity on page e22. Learning Objective: Upon completion of this assessment, successful learners will be able to understand the epidemiological evidence supporting the association between NSAID use and esophageal adenocarcinoma.

    Conflicts of interest The authors disclose no conflicts.

    Funding Supported in part by the Intramural Program of the National Institutes of Health (NIH). The US Multicenter Study was funded by U01-CA57949 (to T.L.V.), U01-CA57983 (to M.D.G.), and U01-CA57923 (to H.A.R). The Los Angeles County Multi-ethnic Study was funded by 3RT-0122 (“Smoking and Risk of Proximal Vs. Distal Gastric Cancer,” to A.H.W.) and 10RT-0251 (“Smoking, microsatellite instability & gastric cancers,” to A.H.W.) from the California Tobacco-Related Research Program and CA59636 (to L.B.) from the National Cancer Institute. The Nova Scotia Barrett Esophagus Study was supported by the Nova Scotia Health Research Foundation (“Molecular mechanisms and lifestyle risk factor interactions in the pathogenesis of human esophageal adenocarcinoma,” N419, to A.G.C.). The Factors Influencing the Barrett’s Adenocarcinoma Relationship Study was funded by an Ireland-Northern Ireland Co-operation Research Project Grant sponsored by the Northern Ireland Research and Development Office, and the Health Research Board, Ireland (All-Ireland case-control study of Oesophageal Adenocarcinoma and Barrett’s Oesophagus, to L.J.M. and Harry Comber). The Australian Study of Esophageal Cancer was supported by the Queensland Cancer Fund and the National Health and Medical Research Council of Australia (program no. 199600, to D.C.W., Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, David M. Purdie, and Penelope M. Webb). The NIH-AARP Diet and Health Study was funded by the Intramural Program of the NIH.

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