OBJECTIVE Germline mutations of the CHEK2 tumor suppressor gene have been found in families with the Li-Fraumeni syndrome (LFS). Patients with LFS experience a variety of cancers, including malignant astrocytomas. We investigated a potential role for a CHEK2 gene polymorphism in glioblastomas. METHODS A genetic polymorphism of the CHEK2 gene (CHEK2 SNP rs2017309 A/T) was genotyped in a series...

Checkpoint kinase 2 (CHEK2) is a DNA damage-activated protein kinase implicated in cell cycle checkpoint control. The significance of CHEK2 alterations for breast cancer incidence and clinical behavior is not clear. In this study we determined the mutational spectrum and the level of promoter hypermethylation of CHEK2 gene in a group of 145 Bulgarian patients with breast cancer. A special empha...

CHEK2 mutations have been reported to be associated with different human cancers. However, the genetic defects distribution and the roles of CHEK2 mutations in gastric cancer carcinogenesis remain poorly understood. In this study, we detected two CHEK2 alleles: a protein truncating (1100delC, IVS2+1G>A) and a missense variant (I157T) in 63 unselected gastric cancer cases and 96 healthy controls...

PURPOSE The pathogenic CHEK2 1100delC variant is firmly established as a breast cancer susceptibility allele. Dutch CHEK2 1100delC breast cancer families frequently also include colorectal cancer cases, and the variant is particularly prevalent among breast cancer families with hereditary breast and colorectal cancer. Yet, it is still unclear whether CHEK2 1100delC also confers a colorectal can...

Germline mutations of the CHEK2 gene have been reported in some myeloid and lymphoid malignancies, but their impact on development of essential thrombocythemia has not been studied. In 16 out of 106 (15.1%) consecutive patients, newly diagnosed with essential thrombocythemia, we found one of four analyzed CHEK2 mutations: I157T, 1100delC, IVS2+1G>A or del5395. They were associated with the incr...

BACKGROUND Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk. METHODS We gen...

Mutations in the CHEK2 gene confer an approximately twofold increase in the risk of cancer in many organs including the breast, colon, kidney, prostate and thyroid. In addition, we have recently identified a positive association of similar magnitude between a CHEK2 mutation and bladder cancer, endometrial cancer and low-grade ovarian cancer (unpublished data). Surveillance is available for most...

The frame-shifting mutation 1100delC in the cell-cycle-checkpoint kinase 2 gene (CHEK2) has been reported to be associated with familial breast cancer in families in which mutations in BRCA1 and BRCA2 were excluded. To investigate the role of this variant as a candidate breast cancer susceptibility allele, we determined its prevalence in 237 breast cancer patients and 331 healthy relatives deri...

Background and aims CHEK2 gene is located on chromosome 22q12.1. and encodes the human analogue of the yeast checkpoint kinases Cds1 and Rad 53. Activation of CHEK2 in response to DNA damage prevents the cell from entering into mitosis. Three founder alleles are present in Poland. Two of these result in a truncated CHEK2 protein IVS2+1G>A in exon 3 and 1100 del C in exon 10, the other, I157T is...

BACKGROUND Checkpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. Previous investigation has established a role for the CHEK2 gene in breast cancer aetiology, but studies have largely been limited to the rare 1100delC mutation. Whether common polymorphisms in this gene influence breast cancer risk remains unkn...