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Observational studies have shown that colonoscopy reduces colorectal cancer (CRC) incidence and mortality in the general population. We aimed to conduct a meta-analysis quantifying the magnitude of protection by colonoscopy, with screening and diagnostic indications, against CRC in patients with non-malignant findings and demonstrating the potentially more marked effect of screening over diagnostic colonoscopy.PubMed, EMBASE, and conference abstracts were searched through 30 April 2015. The primary outcomes were overall CRC incidence and mortality. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effect models.Eleven observational studies with a total of 1,499,521 individuals were included. Pooled analysis showed that colonoscopy was associated with a 61% RR reduction in CRC incidence (RR: 0.39; 95% CI: 0.26–0.60;I2=93.6%) and a 61% reduction in CRC mortality (RR: 0.39; 95% CI: 0.35–0.43;I2=12.0%) in patients with non-malignant findings, although there was high heterogeneity for the outcome of CRC incidence. After excluding one outlier study, there was low heterogeneity for the outcome of incidence (I2=44.7%). Subgroup analysis showed that the effect of screening colonoscopy was more prominent, corresponding to an 89% reduction in CRC incidence (RR: 0.11; 95% CI: 0.08–0.15), in comparison with settings involving diagnostic colonoscopy (RR: 0.51; 95% CI: 0.43–0.59;P<0.001).On the basis of this meta-analysis of observational studies, CRC incidence and mortality in patients with non-malignant findings are significantly reduced after colonoscopy. The effect of screening colonoscopy on CRC incidence is more marked than diagnostic colonoscopy.