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. 2017 Dec;25(12):1345-1353.
doi: 10.1038/s41431-017-0021-2. Epub 2017 Nov 8.

Contribution of germline deleterious variants in the RAD51 paralogs to breast and ovarian cancers

Lisa Golmard  1   2 , Laurent Castéra  3   4 , Sophie Krieger  3   4   5 , Virginie Moncoutier  6 , Khadija Abidallah  6 , Henrique Tenreiro  6 , Anthony Laugé  6 , Julien Tarabeux  6   7 , Gael A Millot  8   9 , André Nicolas  6 , Marick Laé  6 , Caroline Abadie  10 , Pascaline Berthet  11 , Florence Polycarpe  11 , Thierry Frébourg  4   12   13 , Camille Elan  6 , Antoine de Pauw  6 , Marion Gauthier-Villars  6 , Bruno Buecher  6 , Marc-Henri Stern  6   7   14 , Dominique Stoppa-Lyonnet  6   7   15 , Dominique Vaur  3   4 , Claude Houdayer  6   7   15
Affiliations

Contribution of germline deleterious variants in the RAD51 paralogs to breast and ovarian cancers

Lisa Golmard et al. Eur J Hum Genet. 2017 Dec.

Abstract

RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) have recently been involved in breast and ovarian cancer predisposition: RAD51B, RAD51C, and RAD51D in ovarian cancer, RAD51B and XRCC2 in breast cancer. The aim of this study was to estimate the contribution of deleterious variants in the five RAD51 paralogs to breast and ovarian cancers. The five RAD51 paralog genes were analyzed by next-generation sequencing technologies in germline DNA from 2649 consecutive patients diagnosed with breast and/or ovarian cancer. Twenty-one different deleterious variants were identified in the RAD51 paralogs in 30 patients: RAD51B (n = 4), RAD51C (n = 12), RAD51D (n = 7), XRCC2 (n = 2), and XRCC3 (n = 5). The overall deleterious variant rate was 1.13% (95% confidence interval (CI): 0.72-1.55%) (30/2649), including 15 variants in breast cancer only cases (15/2063; 0.73% (95% CI: 0.34-1.11%)) and 15 variants in cases with at least one ovarian cancer (15/570; 2.63% (95% CI: 1.24-4.02%)). This study is the first evaluation of the five RAD51 paralogs in breast and ovarian cancer predisposition and it demonstrates that deleterious variants can be present in breast cancer only cases. Moreover, this is the first time that XRCC3 deleterious variants have been identified in breast and ovarian cancer cases.

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Conflict of interest statement

The authors declare no conflict of interest.

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