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 Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Ku80 is a subunit of the Ku heterodimer that binds to DNA double-strand break ends as part of the non-homologous end joining (NHEJ) pathway. Ku80 is also involved in homologous recombination (HR)  via  its interaction with  BRCA1 . Ku80 is encoded by the  XRCC5  gene that contains a variable number tandem repeat (VNTR) insertion in its promoter region. Different VNTR genotypes can alter  XRCC5  expression and affect Ku80 production, thereby affecting NHEJ and HR pathways. VNTR polymorphism is associated with multiple types of sporadic cancer. In this study, we investigated its potential association with familial breast cancer at the germline level. Using PCR, PAGE, Sanger sequencing, and statistical analyses, we compared VNTR genotypes in the  XRCC5  promoter between healthy individuals and three types of familial breast cancer cases: mutated  BRCA1  ( BRCA1  + ), mutated  BRCA2  ( BRCA2  + ), and wild-type  BRCA1 / BRCA2  ( BRCAx ). We observed significant differences of VNTR genotypes between control and  BRCA1  +  group ( P  < 0.0001) and  BRCA2  +  group ( P  = 0.0042) but not  BRCAx  group ( P  = 0.2185), and the differences were significant between control and cancer-affected  BRCA1  +  cases ( P  < 0.0001) and  BRCA2  +  cases ( P  = 0.0092) but not cancer-affected  BRCAx  cases ( P  = 0.4251). Further analysis indicated that 2R/2R (OR = 1.94, 95%CI = 1.26–2.95,  P  = 0.0096) and 2R/1R (OR = 1.58, 95%CI = 1.11–2.26,  P  = 0.0388) were associated with increased risk but 1R/1R (OR = 0.55, 95%CI = 0.35–0.84,  P  = 0.0196) and 1R/0R (OR = 0, 95%CI = 0–0.29,  P  = 0.0012) were associated with decreased risk in cancer-affected  BRCA1  +  group; 2R/1R (OR = 1.94, 95%CI = 1.14–3.32,  P  = 0.0242) was associated with increased risk in cancer-affected  BRCA2  +  group. No correlation was observed for the altered risk between cancer-affected or -unaffected carriers and between different age of cancer diagnosis in cancer-affected carriers. The frequently observed VNTR association with in  BRCA1  +  and  BRCA2  +  breast cancer group indicates that VNTR polymorphism in the  XRCC5  promoter is associated with altered risk of breast cancer in  BRCA1  +  and  BRCA2  +  carriers.

frontiers in oncology

Differences of Variable Number Tandem Repeats in XRCC5 Promoter Are Associated with Increased or Decreased Risk of Breast Cancer in BRCA Gene Mutation Carriers