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.
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.
Authors: Zsofia K Stadler; Kasmintan A Schrader; Joseph Vijai; Mark E Robson; Kenneth Offit Journal: J Clin Oncol Date: 2014-01-21 Impact factor: 44.544
Authors: Paolo Peterlongo; Irene Catucci; Mara Colombo; Laura Caleca; Eliseos Mucaki; Massimo Bogliolo; Maria Marin; Francesca Damiola; Loris Bernard; Valeria Pensotti; Sara Volorio; Valentina Dall'Olio; Alfons Meindl; Claus Bartram; Christian Sutter; Harald Surowy; Valérie Sornin; Marie-Gabrielle Dondon; Séverine Eon-Marchais; Dominique Stoppa-Lyonnet; Nadine Andrieu; Olga M Sinilnikova; Gillian Mitchell; Paul A James; Ella Thompson; Marina Marchetti; Cristina Verzeroli; Carmen Tartari; Gabriele Lorenzo Capone; Anna Laura Putignano; Maurizio Genuardi; Veronica Medici; Isabella Marchi; Massimo Federico; Silvia Tognazzo; Laura Matricardi; Simona Agata; Riccardo Dolcetti; Lara Della Puppa; Giulia Cini; Viviana Gismondi; Valeria Viassolo; Chiara Perfumo; Maria Antonietta Mencarelli; Margherita Baldassarri; Bernard Peissel; Gaia Roversi; Valentina Silvestri; Piera Rizzolo; Francesca Spina; Caterina Vivanet; Maria Grazia Tibiletti; Maria Adelaide Caligo; Gaetana Gambino; Stefania Tommasi; Brunella Pilato; Carlo Tondini; Chiara Corna; Bernardo Bonanni; Monica Barile; Ana Osorio; Javier Benitez; Luisa Balestrino; Laura Ottini; Siranoush Manoukian; Marco A Pierotti; Alessandra Renieri; Liliana Varesco; Fergus J Couch; Xianshu Wang; Peter Devilee; Florentine S Hilbers; Christi J van Asperen; Alessandra Viel; Marco Montagna; Laura Cortesi; Orland Diez; Judith Balmaña; Jan Hauke; Rita K Schmutzler; Laura Papi; Miguel Angel Pujana; Conxi Lázaro; Anna Falanga; Kenneth Offit; Joseph Vijai; Ian Campbell; Barbara Burwinkel; Anders Kvist; Hans Ehrencrona; Sylvie Mazoyer; Sara Pizzamiglio; Paolo Verderio; Jordi Surralles; Peter K Rogan; Paolo Radice Journal: Hum Mol Genet Date: 2015-06-30 Impact factor: 6.150
Authors: Daniel J Park; Kayoko Tao; Florence Le Calvez-Kelm; Tu Nguyen-Dumont; Nivonirina Robinot; Fleur Hammet; Fabrice Odefrey; Helen Tsimiklis; Zhi L Teo; Louise B Thingholm; Erin L Young; Catherine Voegele; Andrew Lonie; Bernard J Pope; Terrell C Roane; Russell Bell; Hao Hu; Chad D Huff; Jonathan Ellis; Jun Li; Igor V Makunin; Esther M John; Irene L Andrulis; Mary B Terry; Mary Daly; Saundra S Buys; Carrie Snyder; Henry T Lynch; Peter Devilee; Graham G Giles; John L Hopper; Bing-Jian Feng; Fabienne Lesueur; Sean V Tavtigian; Melissa C Southey; David E Goldgar Journal: Cancer Discov Date: 2014-05-02 Impact factor: 39.397
Authors: Florentine S Hilbers; Caro M Meijers; Jeroen F J Laros; Michiel van Galen; Nicoline Hoogerbrugge; Hans F A Vasen; Petra M Nederlof; Juul T Wijnen; Christi J van Asperen; Peter Devilee Journal: PLoS One Date: 2013-01-31 Impact factor: 3.240