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The Czech Republic has one of the highest incidence rates of colorectal cancer (CRC) worldwide. The vast majority of the CRC cases arises sporadically, with susceptibility determined by genetic factors in interaction with an environment. Cell cycle and DNA repair genes play a fundamental role in CRC development and presents many common variants. In the present study, we genotyped common variants in cell cycle and DNA repair genes to assess the influence of genetic variation on the CRC risk, in 614 hospital-based CRC cases and 614 matched controls. Despite a tendency towards a differential distribution of the variant allele frequencies for some cell cycle polymorphisms, none was significantly associated with CRC risk. We observed a differential distribution between cases and controls of major haplotypes arising from the four analysed variants in the TP53 gene. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risk.