• CHEK2
• colorectal cancer
• susceptibility allele
• allelic imbalance

• CHEK2, cell cycle checkpoint kinase 2
• CRC, colorectal cancer
• HBCC, hereditary breast and colorectal cancer phenotype
• HNPCC, hereditary nonpolyposis colorectal cancer
• LFS, Li-Fraumeni syndrome
• MSI, microsatellite instability

Cell cycle checkpoint kinase 2 (CHEK2) is a tumour suppressor involved in the p53 pathway of DNA damage responses. Upon ionizing radiation induced DNA damage, CHEK2 is activated by ataxia telangiectasia mutated (ATM) and is in turn capable of phosphorylating several substrates including Cdc25A, Cdc25C, p53, and BRCA1, leading to cell cycle arrest, apoptosis, and DNA repair (reviewed in Bartek et al¹). A protein truncating mutation, 1100delC, which resides in exon 10 and abolishes the kinase function of CHEK2, has been shown to be significantly associated with a positive family history of breast cancer.^2,3This allele is found with a 1.1–1.4% frequency in the normal population in the European countries studied so far but at a 4.9–5.9% frequency among familial BRCA1/2 negative breast cancer patients.^2,3The 1100delC allele appears to be a low penetrance susceptibility allele for breast cancer, with a twofold increased breast cancer risk for carriers.²Expression of the CHEK2 protein has been shown to be absent or grossly reduced in breast tumours of heterozygous 1100delC mutation carriers,³and loss of the wild-type allele has been reported in a breast tumour and a sarcoma of CHEK2 mutation carriers in Li-Fraumeni syndrome (LFS).⁴

Very recently, the frequency of the 1100delC allele has been suggested to be higher among breast cancer families that also have colorectal cancer (CRC) than in those without CRC, identifying a hereditary breast and colorectal cancer phenotype (HBCC).⁵To evaluate the significance of the 1100delC allele for colorectal cancer we studied the frequency of the 1100delC in 662 colorectal cancer patients, including 149 familial CRC patients. We also studied the allelic imbalance at 1100delC in the colorectal tumours from patients with a germline 1100delC mutation.