English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background  Mutations in the  BRCA1  and  BRCA2  genes are responsible for only a part of hereditary breast cancer (HBC). The origins of "non- BRCA " HBC in families may be attributed in part to rare mutations in genes conferring moderate risk, such as  CHEK2 , which encodes for an upstream regulator of BRCA1. Previous studies have demonstrated an association between  CHEK2  founder mutations and non- BRCA  HBC. However, very few data on the entire coding sequence of this gene are available.    Methods  We investigated the contribution of  CHEK2  mutations to non- BRCA  HBC by direct sequencing of its whole coding sequence in 507 non- BRCA  HBC cases and 513 controls.    Results  We observed 16 mutations in cases and 4 in controls, including 9 missense variants of uncertain consequence. Using both  in silico  tools and an  in vitro  kinase activity test, the majority of the variants were found likely to be deleterious for protein function. One variant present in both cases and controls was proposed to be neutral. Removing this variant from the pool of potentially deleterious variants gave a mutation frequency of 1.48% for cases and 0.29% for controls ( P  = 0.0040). The odds ratio of breast cancer in the presence of a deleterious  CHEK2  mutation was 5.18.    Conclusions  Our 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.

CHEK2 contribution to hereditary breast cancer in non-BRCAfamilies