Aspirin and the risk of colorectal and other digestive tract cancers: an updated meta-analysis through 2019

Background: Aspirin has been associated with a reduced risk of colorectal cancer, and possibly of a few other digestive tract cancers. The quantification of risk reduction and the optimal dose and duration of aspirin use for the prevention of colorectal and other digestive tract cancers remains unclear. Methods: To provide an up-to-date quantification of this association, we conducted a systematic review and meta-analysis of all observational studies on aspirin and cancers of the digestive tract sites published through March 2019. We estimated the pooled relative risk (RR) of cancer for regular aspirin use versus non-use using random-effects models, and, whenever data were available, we investigated the dose- and duration-risk relations. Results: Regular aspirin use is associated with a reduced risk of colorectal cancer [RR = 0.73, 95% confidence interval (CI) = 0.69-0.78, 45 studies], squamous-cell esophageal cancer (RR = 0.67, 95% CI = 0.57-0.79, 13 studies), adenocarcinoma of the esophagus and gastric cardia (RR = 0.61, 95% CI = 0.49-0.77, 10 studies), stomach cancer (RR = 0.64, 95% CI = 0.51-0.82, 14 studies), hepato-biliary tract cancer (RR = 0.62, 95% CI = 0.44-0.86, five studies), and pancreatic cancer (RR = 0.78, 95% CI = 0.68-0.89, 15 studies), but not of head and neck cancer (RR = 0.94, 95% CI = 0.76-1.16, 10 studies). The associations are somewhat stronger in case-control than in cohort and nested case-control studies and are characterized by some between-study heterogeneity. Risk estimates are consistent across sex, geographical areas, and other selected covariates. For colorectal cancer, an aspirin dose between 75 and 100 mg/day conveys a risk reduction of 10%, and a dose of 325 mg/day of 35%. For all neoplasms, except head and neck cancer, inverse duration-risk relations with aspirin use are found. Conclusion: The present comprehensive meta-analysis supports and further quantifies the inverse association between regular aspirin use and the risk of colorectal and other digestive tract cancers, including some rare ones. The favorable effect of aspirin increases with longer duration of use, and, for colorectal cancer, with increasing dose.