Rare variants in XRCC2 as breast cancer susceptibility alleles Journal Article


Authors: Hilbers, F. S.; Wijnen, J. T.; Hoogerbrugge, N.; Oosterwijk, J. C.; Collee, M. J.; Peterlongo, P.; Radice, P.; Manoukian, S.; Feroce, I.; Capra, F.; Couch, F. J.; Wang, X.; Guidugli, L.; Offit, K.; Shah, S.; Campbell, I. G.; Thompson, E. R.; James, P. A.; Trainer, A. H.; Gracia, J.; Benítez, J.; van Asperen, C. J.; Devilee, P.
Article Title: Rare variants in XRCC2 as breast cancer susceptibility alleles
Abstract: Background: Recently, rare germline variants in XRCC2 were detected in non-BRCA1/2 familial breast cancer cases, and a significant association with breast cancer was reported. However, the breast cancer risk associated with these variants needs further evaluation. Methods: The coding regions and exon-intron boundaries of XRCC2 were scanned for mutations in an international cohort of 3548 non-BRCA1/2 familial breast cancer cases and 1435 healthy controls using various mutation scanning methods. Predictions on functional relevance of detected missense variants were obtained from three different prediction algorithms. Results: The only protein-truncating variant detected was found in a control. Rare non-protein-truncating variants were detected in 20 familial cases (0.6%) and nine healthy controls (0.6%). Although the number of variants predicted to be damaging or neutral differed between prediction algorithms, in all instances these categories were evenly represented among cases and controls. Conclusions: Our data do not confirm an association between XRCC2 variants and breast cancer risk, although a relative risk smaller than two could not be excluded. Variants in XRCC2 are unlikely to explain a substantial proportion of familial breast cancer.
Keywords: controlled study; unclassified drug; gene mutation; major clinical study; allele; cancer susceptibility; breast cancer; nuclear protein; genetic association; genetic variability; x ray repair cross complementing 2 protein
Journal Title: Journal of Medical Genetics
Volume: 49
Issue: 10
ISSN: 0022-2593
Publisher: BMJ Publishing Group Ltd.  
Date Published: 2012-10-01
Start Page: 618
End Page: 620
Language: English
DOI: 10.1136/jmedgenet-2012-101191
PROVIDER: scopus
PUBMED: 23054243
DOI/URL:
Notes: --- - "Export Date: 2 January 2013" - "CODEN: JMDGA" - "Source: Scopus"
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MSK Authors
  1. Kenneth Offit
    528 Offit
  2. Sohela Shah
    15 Shah