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Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the US. To systematically review the effectiveness, test accuracy, and harms of screening for CRC to inform the US Preventive Services Task Force. MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2015, to December 4, 2019; surveillance through March 26, 2021. English-language studies conducted in asymptomatic populations at general risk of CRC. Two reviewers independently app