Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers.

Authors:
Antonis C Antoniou Christiana Kartsonaki Olga M Sinilnikova Penny Soucy Lesley McGuffog Sue Healey Andrew Lee Paolo Peterlongo Siranoush Manoukian Bernard Peissel Daniela Zaffaroni Elisa Cattaneo Monica Barile Valeria Pensotti Barbara Pasini Riccardo Dolcetti Giuseppe Giannini Anna Laura Putignano Liliana Varesco Paolo Radice Phuong L Mai Mark H Greene Irene L Andrulis Gord Glendon Hilmi Ozcelik Mads Thomassen Anne-Marie Gerdes Torben A Kruse Uffe Birk Jensen Dorthe G Crüger Maria A Caligo Yael Laitman Roni Milgrom Bella Kaufman Shani Paluch-Shimon Eitan Friedman Niklas Loman Katja Harbst Annika Lindblom Brita Arver Hans Ehrencrona Beatrice Melin Katherine L Nathanson Susan M Domchek Timothy Rebbeck Ania Jakubowska Jan Lubinski Jacek Gronwald Tomasz Huzarski Tomasz Byrski Cezary Cybulski Bohdan Gorski Ana Osorio Teresa Ramón y Cajal Florentia Fostira Raquel Andrés Javier Benitez Ute Hamann Frans B Hogervorst Matti A Rookus Maartje J Hooning Marcel R Nelen Rob B van der Luijt Theo A M van Os Christi J van Asperen Peter Devilee Hanne E J Meijers-Heijboer Encarna B Gómez Garcia Susan Peock Margaret Cook Debra Frost Radka Platte Jean Leyland D Gareth Evans Fiona Lalloo Ros Eeles Louise Izatt Julian Adlard Rosemarie Davidson Diana Eccles Kai-ren Ong Jackie Cook Fiona Douglas Joan Paterson M John Kennedy Zosia Miedzybrodzka Andrew Godwin Dominique Stoppa-Lyonnet Bruno Buecher Muriel Belotti Carole Tirapo Sylvie Mazoyer Laure Barjhoux Christine Lasset Dominique Leroux Laurence Faivre Myriam Bronner Fabienne Prieur Catherine Nogues Etienne Rouleau Pascal Pujol Isabelle Coupier Marc Frénay John L Hopper Mary B Daly Mary B Terry Esther M John Saundra S Buys Yosuf Yassin Alexander Miron David Goldgar Christian F Singer Muy-Kheng Tea Georg Pfeiler Anne Catharina Dressler Thomas v O Hansen Lars Jønson Bent Ejlertsen Rosa Bjork Barkardottir Tomas Kirchhoff Kenneth Offit Marion Piedmonte Gustavo Rodriguez Laurie Small John Boggess Stephanie Blank Jack Basil Masoud Azodi Amanda Ewart Toland Marco Montagna Silvia Tognazzo Simona Agata Evgeny Imyanitov Ramunas Janavicius Conxi Lazaro Ignacio Blanco Paul D P Pharoah Lara Sucheston Beth Y Karlan Christine S Walsh Edith Olah Aniko Bozsik Soo-Hwang Teo Joyce L Seldon Mary S Beattie Elizabeth J van Rensburg Michelle D Sluiter Orland Diez Rita K Schmutzler Barbara Wappenschmidt Christoph Engel Alfons Meindl Ina Ruehl Raymonda Varon-Mateeva Karin Kast Helmut Deissler Dieter Niederacher Norbert Arnold Dorothea Gadzicki Ines Schönbuchner Trinidad Caldes Miguel de la Hoya Heli Nevanlinna Kristiina Aittomäki Martine Dumont Jocelyne Chiquette Marc Tischkowitz Xiaoqing Chen Jonathan Beesley Amanda B Spurdle Susan L Neuhausen Yuan Chun Ding Zachary Fredericksen Xianshu Wang Vernon S Pankratz Fergus Couch Jacques Simard Douglas F Easton Georgia Chenevix-Trench

Hum Mol Genet 2011 Aug 18;20(16):3304-21. Epub 2011 May 18.

Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.

Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

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http://dx.doi.org/10.1093/hmg/ddr226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652640PMC
August 2011
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