Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis

Abstract

Use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of gastric or oesophageal adenocarcinomas. We examined the association between self-reported use of aspirin or non-aspirin NSAIDs in the earlier 12 months and gastric non-cardia (N=182), gastric cardia (N=178), and oesophageal adenocarcinomas (N=228) in a prospective cohort (N=311 115) followed for 7 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) come from Cox models adjusted for potential confounders. Use of any aspirin (HR, 95% CI: 0.64, 0.47-0.86) or other NSAIDs (0.68, 0.51-0.92) was associated with a significantly lower risk of gastric non-cardia adenocarcinoma. Neither aspirin (0.86, 0.61-1.20) nor other NSAIDs (0.91, 0.67-1.22) had a significant association with gastric cardia cancer. We found no significant association between using aspirin (1.00, 0.73-1.37) or other NSAIDs (0.90, 69-1.17) and oesophageal adenocarcinoma. We also performed a meta-analysis of the association between the use of NSAIDs and risk of gastric and oesophageal adenocarcinoma. In this analysis, aspirin use was inversely associated with both gastric and oesophageal adenocarcinomas, with summary odds ratios (95% CI) for non-cardia, cardia, and oesophageal adenocarcinomas of 0.64 (0.52-0.80), 0.82 (0.65-1.04), and 0.64 (0.52-0.79), respectively. The corresponding numbers for other NSAIDs were 0.68 (0.57-0.81), 0.80 (0.67-0.95), and 0.65 (0.50-0.85), respectively.

Figure 1

Forest plots for the association between any aspirin (A) or non-aspirin NSAID (B) use and risk of oesophageal, gastric cardia, or gastric non-cardia cancer. Summary estimates and study weights (proportional to symbol size) come from random effects models. Studies are listed by the last name of the first author and Abnet refers to this study. We used the broadest measure of NSAID exposure and multivariable-adjusted estimates whenever possible. To make the exposure measures more comparable, we generated new combined estimates of effect when the published estimates were stratified on dose or duration, and this is indicated by an asterisk after the first author's name. Gastric NOS means that the location of the tumours within the stomach was not specified. The summary estimate for all studies included in this figure was 0.72 (0.67–0.79).

Figure 2

Begg funnel plot with pseudo 95% confidence intervals for all estimates included in the meta-analysis of NSAID use and oesophageal or stomach adenocarcinoma. Both the Begg test (P=0.010) and the Egger test (P=0.001) suggested publication bias, but, dropping the studies with a standard error greater than 0.2 (N=20) or a log OR less than −0.50 (N=14) left the association essentially unchanged. Therefore, publication bias probably had little effect on the summary estimates.