Prospective data examining the association of aspirin use, according to dose and duration, with long-term risk of gastric adenocarcinoma in non-Asian cohorts are lacking. We evaluated the association between aspirin use and risk of gastric adenocarcinoma in two large prospective U.S. cohort studies, the Nurses' Health Study and the Health Professionals Follow-up Study. Cox proportional hazards regression models were used to calculate multivariable adjusted HRs and 95% confidence intervals (CI). Among the 159,116 participants, we documented 316 gastric adenocarcinoma cases (176 women, 140 men) over 34 years encompassing 4.5 million person-years. Among women, regular aspirin use (at least two times or more per week) was significantly associated with lower risk of gastric adenocarcinoma (multivariable HR, 0.52; 95% CI, 0.37–0.73) compared with nonregular use. However, regular aspirin use was not associated with gastric adenocarcinoma risk among men (multivariable HR, 1.08; 95% CI, 0.77–1.52; Pheterogeneity for sex = 0.003). Among women, the lower risk of gastric adenocarcinoma was more apparent with increasing duration of aspirin use (Ptrend < 0.001) and more than five tablets per week (multivariable HR, 0.51; 95% CI, 0.31–0.84). Regular, long-term aspirin use was associated with lower risk of gastric adenocarcinoma among women, but not men. The benefit appeared after at least 10 years of use and was maximized at higher doses among women. The heterogeneity by sex in the association of aspirin use with risk of gastric adenocarcinoma requires further investigation.

Prevention Relevance:

Novel prevention is urgently needed to reduce incidence and mortality of gastric cancer. We found that regular aspirin use was associated with lower risk of gastric adenocarcinoma among women, but not men. The benefit appeared after at least 10 years of use and was maximized at higher doses among women.

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