Objective: The aim of this study was to determine whether six genetic polymorphisms confer susceptibility to colorectal cancer (CRC). Methods: A systematic search for candidate genes of CRC was performed among several online databases, including PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang online libraries. After a comprehensive filtering procedure, we harvested five genes, including MGMT (rs12917 and rs2308321), ADH1B (rs1229984), SOD2 (rs4880), XPC (rs2228001), and PPARG (rs1801282). Using the REVMAN and Stata software, six meta-analyses were conducted for associations between CRC and the just-mentioned genetic variants. Results: A total of 34 comparative studies among 17,289 cases and 54,927 controls were involved in our meta-analyses. Significant association was found between ADH1B rs1229984 polymorphism and CRC ( p = 0.03, odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.01-1.36). We also found significant association between PPARG rs1801282 polymorphism and CRC ( p = 0.004, OR = 1.498, 95% CI = 1.139-1.970), and this significant association is specific in Caucasians ( p = 0.004, OR = 1.603, 95% CI = 1.165-2.205). Conclusions: The current meta-analysis has established that ADH1B (rs1229984) and PPARG (rs1801282) are two risk variants of CRC.