The CHEK2 gene I157T mutation and other alterations in its proximity increase the risk of sporadic colorectal cancer in the Czech population.

Checkpoint kinase 2 (CHEK2) gene codes for an important mediator of DNA damage response pathway. Its mutations increase risk of several types of cancer. We analysed selected CHEK2 mutations in 631 Czech colorectal cancer (CRC) patients. The increased risk of CRC was associated with mutations in CHEK2 gene region involving fork head-associated domain [39/631 (6.2%) cases versus 19/683 (2.8%) controls; odds ratio (OR)=2.3; 95% confidence interval (CI)=1.3-4.0; p=0.003], and with the most frequent I157T mutation [30/631 (4.8%) cases versus 17/683 (2.5%) controls; OR=2.0; 95% CI=1.1-3.6; p=0.03]. Prevalence of 1100delC mutation in CRC patients (4/631) did not differ from that in the control population (2/730; p=0.4). The deletion of 5395 bp was not found in any of the successfully analysed CRC cases. We observed no association of analysed mutations with CRC family history. We conclude that the I157T and other alterations in its proximity predispose to sporadic but not to familial CRC in the Czech population.