Aspirin and Risk of Gastric Cancer After Helicobacter Pylori Eradication

A Territory-Wide Study

Ka Shing Cheung; Esther W. Chan; Angel Y. S. Wong; Lijia Chen; Wai Kay Seto; Ian C. K. Wong; Wai K. Leung


J Natl Cancer Inst. 2018;110(7):743-749. 

In This Article

Abstract and Introduction


Background: Despite successful H. pylori (HP) eradication, some individuals remain at risk of developing gastric cancer (GC). Previous studies showed that aspirin was associated with a reduced GC risk. However, whether aspirin can reduce GC risk in HP-eradicated subjects remains unknown. We aimed to determine the chemopreventive effect of aspirin in HP-eradicated subjects.

Methods: We identified subjects who had received a prescription of clarithromycin-based triple therapy for HP between 2003 and 2012 from a territory-wide health care database. The observation period started from commencement of HP therapy (index date), and the follow-up was censored at the end of the study (December 2015), death, or GC diagnosis. Aspirin use was defined as use once or more often weekly. Subjects who failed HP eradication or were diagnosed with GC within 12 months of HP therapy were excluded. The hazard ratio (HR) of GC with aspirin use was calculated by Cox model with Propensity Score adjustment for age, sex, comorbidities, and concurrent medications. All statistical tests were two-sided.

Results: The median follow-up was 7.6 years (interquartile range [IQR] = 5.1–10.3 years), and 169 (0.27%) out of 63 605 patients developed GC. The incidence rate of GC was 3.5 per 10 000 person-years. Aspirin use was associated with a reduced GC risk (HR = 0.30, 95% confidence interval [CI] = 0.15 to 0.61). The risk of GC decreased with increasing frequency, duration, and dose of aspirin (all P trend < .001).

Conclusions: Aspirin use was associated with a frequency-, dose-, and duration-dependent reduction in GC risk after HP eradication. The effect was most prominent in those who used aspirin daily or for five or more years.


Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related mortality in the world.[1] Helicobacter pylori (H. pylori) infection is a major gastric carcinogen, which triggers and promotes the Correa's gastric carcinogenesis cascade.[2] Individuals infected with H. pylori have a more than threefold increase in risk of gastric cancer,[3] and previous meta-analyses have shown that the risk of gastric cancer development was reduced by 33% to 47% after H. pylori eradication.[4,5] However, the role of other modifiable risk factors, particularly the role of medications on subsequent risk of gastric cancer development, has not been thoroughly examined.

Meta-analyses of observational studies suggest that aspirin reduces gastric cancer risk, while long-term follow-up of randomized trials of aspirin in preventing cardiovascular events shows a statistically nonsignificant trend favoring reduction in gastric cancer risk.[6,7] With low-dose aspirin, the chemopreventive effect is unlikely to be mediated solely through cyclooxygenase (COX)-2 inhibition. Other non-COX-related pathways have been proposed, such as phosphatidylinositol 3-kinase (PI3K),[8,9] nuclear factor (NF)–κB,[10] Wnt-ß-catenin, extracellular signal-regulated kinase (ERK), and activated protein 1 (AP-1),[11] which increases the complexity underlying the chemopreventive effects of low-dose aspirin.

To date, most published studies on the role of aspirin in gastric chemoprevention included both H. pylori–infected and H. pylori–negative subjects. Only a few studies with limited sample size have performed stratified analysis according to H. pylori statuses; they showed that the protective effect of aspirin was larger in H. pylori–infected subjects.[12–14] No study has attempted to determine the role of aspirin in gastric cancer development after H. pylori eradication. In addition, the dose- and duration-benefit relationships remain largely elusive.[15] As aspirin is also associated with an increased risk of gastrointestinal bleeding, particularly in H. pylori–infected subjects, the actual beneficial effects of aspirin as chemoprevention remain to be determined.[16]

We aimed to determine the role of aspirin in gastric cancer development in a large cohort of H. pylori–infected subjects who had received H. pylori eradication therapy.