Nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric adenocarcinomas in Los Angeles County

Background: Nonsteroidal anti-inflammatory drug (NSAID) use has been associated with a reduced risk of colon cancer; further epidemiologic data appear consistent for stomach and esophageal adenocarcinomas. Yet, data on potential confounding effects by upper gastrointestinal tract (UGI) disorders on adenocarcinomas of the UGI are limited. Methods: This study recruited newly diagnosed patients with esophageal adenocarcinoma (n = 220), gastric cardia adenocarcinoma (n = 277), or distal gastric adenocarcinoma (n = 441) as well as 1,356 control subjects in Los Angeles County. Unconditional multivariable logistic regression analyses were done to evaluate the association between regular NSAID use, at least two pills per week for 1 month, and these cancers. Results: Duration of regular use of aspirin and nonaspirin NSAIDs was associated with reduced relative odds of distal gastric adenocarcinoma [> 5 years use versus no regular use: odds ratio (OR), 0.61; 95% confidence interval, 0.40-0.92; P-trend = 0.0091 and esophageal adenocarcinoma (OR, 0.60; 95% confidence interval, 0.38-0.95; P-tnend = 0.04) in multivariable models that included history of UGI disorders and other potential confounding factors. Daily regular use was also associated with statistically significant reduced ORs of these two tumor types. No significant heterogeneity in risk estimates was noted after stratification by history of UGI disorders for any of the sites studied. However, irregular users of NSAIDs also had reduced risk of these cancers when compared with nonusers. Conclusions: Results from this study support an inverse association between regular NSAID use and risk of esophageal and distal gastric adenocarcinomas in individuals with and without a history of UGI disorders with long duration and daily use, providing the greatest risk reduction. Reduced risk in irregular users suggests that factors other than an effect on cyclooxygenase may also be important.