Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations

  title={Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations},
  author={The Polish Breast Cancer Consortium},
  journal={Nature Genetics},
Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer1, but account for only a small fraction of breast cancer susceptibility1,2. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show that CHEK2*1100delC, a truncating variant that abrogates the kinase activity6, has a frequency of 1.1… 
Absence of the CHEK2 c.1100delC mutation in familial breast and ovarian cancer in Colombia: a case-control study
The results suggest that the CHEK2 c.1100delC mutation is not a risk factor for genetic susceptibility to familial breast or ovarian cancer in the Colombian population, showing the importance of considering ethnic background before offering a genetic test.
Two new CHEK2 germ-line variants detected in breast cancer/sarcoma families negative for BRCA1, BRCA2, and TP53 gene mutations
The identification of two previously unreported CHEK2 variants, including a truncating mutation leading to constitutional haploinsufficiency, in individuals belonging to families selected for breast cancer/sarcoma phenotype, supports the hypothesis that the CHEk2 gene may act as a factor contributing to individual tumor development in peculiar familial backgrounds.
Identification of a novel BRCA2 and CHEK2 A-C-G-C haplotype in Turkish patients affected with breast cancer.
The results suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to an unexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role in the development and prognosis of breast cancer.
BRCA1/BRCA2 rearrangements and CHEK2 common mutations are infrequent in Italian male breast cancer cases
It is suggested that screening of BRCA1/2 rearrangements is not advantageous in MBC cases not belonging to high-risk breast cancer families and that common CHEK2 mutations play an irrelevant role in M BC predisposition in Italy.
CHEK2 contribution to hereditary breast cancer in non-BRCA families
This work indicates that a variety of deleterious CHEK2 alleles make an appreciable contribution to breast cancer susceptibility, and their identification could help in the clinical management of patients carrying a CHEk2 mutation.
Mutation screening of the BARD1 gene: evidence for involvement of the Cys557Ser allele in hereditary susceptibility to breast cancer
Colocalisation of BARD1 with BRCA1 and RAD51 in response to DNA damage indicates a role in DNA repair, which is supported by the recent research on DNA repair and cell cycle regulation.
BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India.
This is the first study from South India, on BRCA1, BRCa2 & CHEK2 (1100 del C) mutations in patients with a family history of breast and/or ovarian cancer and early onset breast/ovarian cancer, using the sensitive DHPLC approach.
Frequency of CHEK2 mutations in a population based, case–control study of breast cancer in young women
The CHEK2 variants are rare in the western Washington population and, based on accumulated evidence across studies, are unlikely to be major breast cancer susceptibility genes, so screening for the 1100delC variant may have limited usefulness in breast cancer prevention programs in the USA.
Absence of CHEK2 1100delC mutation in familial breast cancer cases from a South American population
A specific variant in this gene, 1100delC, has been found to increase breast cancer susceptibility among familial breast cancer cases not attributable to mutations in BRCA1/2 and this variant has been estimated to be associated with an approximately 1.5–2.0 fold increased risk in female breast cancer Cases with a positive family history.
Germline CHEK2 mutations and colorectal cancer risk: different effects of a missense and truncating mutations?
It is concluded that the I157T mutation increases the risk of colorectal cancer in the population, but that truncating mutations may confer a lower risk or no increase in risk.