Analýza mutace c.1100delC genu CHEK2 v populaci pacientů se sporadickým karcinomem kolorekta a familiární adenomatózní polypózou

Backgrounds: Czech republic belongs to the countries with the highest incidence of colorectal cancer in both male and female population. The vast majority of colorectal cancer diagnoses arise in a form of sporadic disease. The hereditary predisposition for colorectal cancer development could be found in about 5%. Along with mutations in the major predisposing genes (APC, MLH1, MSH2, MSH6, SMALM, BMPR1a), the role of mutations in low penetrance genes is intensively studied. Recently it has been found that the frame-shifting CHEK2 c.1100delC mutation contributes to the development of hereditary breast and colorectal cancer syndrome (HBCC). Methods: We have performed mutation analysis of pathogenic CHEK2 allele c. 1100delC in 546 patients including 433 colorectal cancer patients and 113 patients with familial adenomatous polyposis (FAP). Mutation analysis was based on DHPLC prescreening, mutations were confirmed by sequencing. Results: We have characterized 3 mutation carriers, all in the colorectal cancer patients' cohort (0.7%). Conclusion: Based on our data we can speculate that Czech Republic belongs to countries with low occurrence of CHEK2 c. 1100delC allele, which therefore rarely contributes to the development of colorectal cancer and plays an insignificant role in cancer development in patients with FAP/AFAP.