Dose-Risk and Duration-Risk Relationships between Aspirin and Colorectal Cancer: A Meta-Analysis of Published Cohort Studies

Abstract
Background: In previous meta-analyses, aspirin use has been associated with reduced risk of colorectal cancer. However, uncertainty remains on the exact dose-risk and duration-risk relationships. Methods: We identified studies by searching several English and Chinese electronic databases and reviewing relevant articles. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Subgroup analyses were conducted to explore possible heterogeneity among studies. Potential heterogeneity was calculated as Q statistic and I-2 value. Publication bias was evaluated using funnel plots and quantified by the Begg's and Egger's test. Results: Twelve studies were included in this meta-analysis. An inverse association between aspirin use and colorectal cancer was observed in both the overall group (RR = 0.74, 95% CI 0.64-0.83 for aspirin dose; RR = 0.80, 95% CI 0.75-0.85 for frequency of aspirin use; RR = 0.75, 95% CI 0.68-0.81 for years of aspirin use) and subgroups stratified by sex and cancer site. The dose-response meta-analysis showed that there was a 20% statistically significant decreased risk of colorectal cancer for 325 mg aspirin per day increment, 18% decreased risk for 7 times aspirin per week increment and 18% decreased risk for 10 years aspirin increment. Conclusion: Long-term (>5 years), low-dose (75-325 mg per day) and regular aspirin use (2-7 times per week) can effectively reduce the risk of colorectal cancer.