Frequency-Risk and Duration-Risk Relationships between Aspirin Use and Gastric Cancer: A Systematic Review and Meta-Analysis

Background: Although previous meta-analyses have suggested an association between aspirin use and risk of gastric cancer, current evidence is inconsistent. Additionally, it remains unclear whether there are frequency-risk and duration-risk relationships and if a threshold of effect exists. Methods: We identified studies by searching MEDLINE and PUBMED databases and reviewing relevant articles. We derived the summary risk estimates using fixed-effects or random-effects model based on homogeneity analysis. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Potential heterogeneity was tested using the Q statistic and quantified with the I 2 statistic. Subgroup analyses and Galbraith plots were used to explore the potential sources of heterogeneity. Publication bias was evaluated with funnel plots and quantified by the Begg's and Egger's test. Results: Fifteen studies were included in this meta-analysis. There was an overall 29% reduced risk of gastric cancer corresponding to aspirin use (RR = 0.71, 95% CI 0.60-0.82). We found there are nonlinear frequency-risk and linear duration-risk relations between aspirin use and gastric cancer. A monotonically decreasing relation was observed only for low-frequency (<= 4.5 times/week) aspirin intake (10% decreased risk for once/week, 19% for twice/week and 29% for 4.5 times/week), and the frequency threshold of aspirin use is 4.5 times per week. Regarding those with duration of aspirin use, there was a tendency towards stronger risk reduction of gastric cancer for longer aspirin use (10% decreased risk for 4 years, 19% for 8 years and 28% for 12 years), and no duration threshold was observed. Conclusion: Our findings suggest that long-term (>= 4 years) and low-frequency (1-4.5 times per week) aspirin use is associated with a statistically significant, dose-dependent reduction in the risk of gastric cancer.