Twenty-one studies were included in the review, comprising 12 case-control studies, one nested case-control and eight cohort studies. The number of study participants was reported in such a way that the overall number of participants across studies could not be calculated.
Non-steroidal anti-inflammatory drug (NSAID) use was found to reduce the incidence of gastric cancer by 21% for the unadjusted analyses (RR 0.79, 95% CI 0.73 to 0.86; I2=71.8%; 16 studies) and by 29% for the adjusted data (RR 0.71, 95% CI 0.64 to 0.79; I2=59.8%; 18 studies). Give the heterogeneity, random-effects models were used to pool the data. Significant publication bias was identified (p<0.01); following application of the trim-and-fill method, smaller reductions in risk of gastric cancer were produced (summary crude RR 0.89, 95%CI 0.83 to 0.97 and adjusted RR 0.81, 95%CI 0.73 to 0.89).
The subgroup analyses showed similar effects for study design (for both crude and adjusted data) and type of NSAID (crude data only). The pooled analysis of adjusted data showed a stronger protective effect from aspirin (RR 0.69, 95%CI: 0.55, 0.86), although the seven contributing studies were highly heterogeneous (I2=80.6%). The analyses by cancer site found a stronger protective effect for non-cardia cancers with NSAIDs for both crude and adjusted data (reductions in incidence of 24% (95% CI 16 to 31) for the crude data and 37% (95% CI 30 to 43) for the adjusted data, although the crude data were fairly heterogeneous (I2=60.5%). Stronger effects were identified for hospital-based studies, with reduction in cancer incidence of 35% (95% CI 19 to 48; four studies) for crude data and 39% (95%CI 24 to 51; three studies) for adjusted data, but the number of studies was small.