Chemoprevention of colorectal cancer in general population and high-risk population: a systematic review and network meta-analysis

Background:Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer(CRC).We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.Methods:We searched PubMed,Embase,and the Cochrane Library for studies published in English until October 31,2021 that fit our inclusion criteria.We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents(low-dose aspirin[Asp],high-dose Asp,cyclooxygenase-2 inhibitors[coxibs],calcium,vitamin D,folic acid,ursodeoxycholic acid[UDCA],estrogen,and progesterone,alone or in combination)for preventing colorectal adenoma and CRC.Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.Results:Thirty-two randomized controlled trials(278,694 participants)comparing 13 different interventions were included.Coxibs significantly reduced the risk of colorectal adenoma(risk ratio[RR]:0.59,95%confidence interval[CI]:0.44–0.79,six trials involving 5486 participants),advanced adenoma(RR:0.63,95%CI:0.43–0.92,four trials involving 4723 participants),and metachronous adenoma(RR:0.58,95%CI:0.43–0.79,five trials involving 5258 participants)compared with placebo.Coxibs also significantly increased the risk of severe adverse events(RR:1.29,95%CI:1.13–1.47,six trials involving 7109 participants).Other interventions,including Asp,folic acid,UDCA,vitamin D,and calcium,did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.Conclusions:Considering the balance between benefits and harms,regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence.Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.