Cumulative Dose Threshold for the Chemopreventive Effect of Aspirin Against Gastric Cancer

Many studies have found evidence that aspirin has protective effects against certain cancers, but quantitative dose–response data have been available only on a limited basis. This study aimed to confirm the dose–response relationship of aspirin usage and gastric cancer and to estimate the cumulative dose threshold of aspirin to achieve protective effects against gastric cancer in the general population. A total of 461,489 individuals in a population-based longitudinal cohort provided by the National Health Insurance Services (NHIS) in the Republic of Korea were observed from 2007 to 2012 to identify gastric cancer incident cases. The pharmacy claims data of these individuals from 2002 to 2006 were reviewed to assess cumulative medication exposure using the defined daily dose (DDD) system. Hazard ratios (HRs) of aspirin use for gastric cancer were estimated using multivariate Cox Proportional Hazard regression. Sensitivity analyses, including propensity-score matching and a nested case–control design, were performed to evaluate the variability caused by study design. A total of 5674 incident gastric cancers were identified from 2,965,500 person-years of follow-up observation, giving an overall incidence rate of 191.00 gastric cancers per 100,000 person-years. Compared to non-users, those with aspirin use of ≥3 DDD-years showed a statistically significant protective effect of aspirin use against gastric cancer; the adjusted HR (95% confidence intervals) were 0.79 (0.63–0.98) and 0.63 (0.48–0.83) for those with aspirin use of 3–4 DDD-years and 4–5 DDD-years, respectively (P for trend 3 DDD-years.