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.

Institute of Biochemistry and Experimental Oncology 1st Faculty of Medicine Charles University Prague U Nemocnice 5 128 53 Prague 2 Czech Republic

References provided by Crossref.org

CHEK2 Germline Variants in Cancer Predisposition: Stalemate Rather than Checkmate

Validation of CZECANCA (CZEch CAncer paNel for Clinical Application) for targeted NGS-based analysis of hereditary cancer syndromes

Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma

Mutation Analysis of the RAD51C and RAD51D Genes in High-Risk Ovarian Cancer Patients and Families from the Czech Republic

Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint