Rare mutations in XRCC2 increase the risk of breast cancer.

نویسندگان

  • D J Park
  • F Lesueur
  • T Nguyen-Dumont
  • M Pertesi
  • F Odefrey
  • F Hammet
  • S L Neuhausen
  • E M John
  • I L Andrulis
  • M B Terry
  • M Daly
  • S Buys
  • F Le Calvez-Kelm
  • A Lonie
  • B J Pope
  • H Tsimiklis
  • C Voegele
  • F M Hilbers
  • N Hoogerbrugge
  • A Barroso
  • A Osorio
  • G G Giles
  • P Devilee
  • J Benitez
  • J L Hopper
  • S V Tavtigian
  • D E Goldgar
  • M C Southey
چکیده

An exome-sequencing study of families with multiple breast-cancer-affected individuals identified two families with XRCC2 mutations, one with a protein-truncating mutation and one with a probably deleterious missense mutation. We performed a population-based case-control mutation-screening study that identified six probably pathogenic coding variants in 1,308 cases with early-onset breast cancer and no variants in 1,120 controls (the severity grading was p < 0.02). We also performed additional mutation screening in 689 multiple-case families. We identified ten breast-cancer-affected families with protein-truncating or probably deleterious rare missense variants in XRCC2. Our identification of XRCC2 as a breast cancer susceptibility gene thus increases the proportion of breast cancers that are associated with homologous recombination-DNA-repair dysfunction and Fanconi anemia and could therefore benefit from specific targeted treatments such as PARP (poly ADP ribose polymerase) inhibitors. This study demonstrates the power of massively parallel sequencing for discovering susceptibility genes for common, complex diseases.

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منابع مشابه

Polymorphisms in RAD51, XRCC2, and XRCC3 are not related to breast cancer risk.

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Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer.

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Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Pol...

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عنوان ژورنال:
  • American journal of human genetics

دوره 90 4  شماره 

صفحات  -

تاریخ انتشار 2012