Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

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title = "Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers",
abstract = "Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10(-4)). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10(-5), P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df P = 0.007; rs1292011 2df P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10(-5)) and there was marginal evidence of association with ER- negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.",
author = "Antoniou, {Antonis C.} and Kuchenbaecker, {Karoline B.} and Penny Soucy and Jonathan Beesley and Xiaoqing Chen and Lesley McGuffog and Andrew Lee and Daniel Barrowdale and Sue Healey and Sinilnikova, {Olga M.} and Caligo, {Maria A.} and Niklas Loman and Katja Harbst and Annika Lindblom and Brita Arver and Richard Rosenquist and Per Karlsson and Kate Nathanson and Susan Domchek and Tim Rebbeck and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska and Katarzyna Durda and Elzbieta Zlowowcka-Perlowska and Ana Osorio and Mercedes Duran and Raquel Andres and Javier Benitez and Ute Hamann and Hogervorst, {Frans B.} and {van Os}, {Theo A.} and Senno Verhoef and Meijers-Heijboer, {Hanne E. J.} and Juul Wijnen and Garcia, {Encarna B. Gomez} and Ligtenberg, {Marjolijn J.} and Mieke Kriege and Margriet Collee and Ausems, {Margreet G. E. M.} and Oosterwijk, {Jan C.} and Susan Peock and Debra Frost and Ellis, {Steve D.} and Radka Platte and Elena Fineberg and Evans, {D. Gareth} and Fiona Lalloo and Chris Jacobs and Ros Eeles and Julian Adlard and Rosemarie Davidson and Trevor Cole and Jackie Cook and Joan Paterson and Fiona Douglas and Carole Brewer and Shirley Hodgson and Morrison, {Patrick J.} and Lisa Walker and Rogers, {Mark T.} and Alan Donaldson and Huw Dorkins and Godwin, {Andrew K.} and Betsy Bove and Dominique Stoppa-Lyonnet and Claude Houdayer and Bruno Buecher and {de Pauw}, Antoine and Sylvie Mazoyer and Alain Calender and Melanie Leone and {Bressac-de Paillerets}, Brigitte and Olivier Caron and Hagay Sobol and Marc Frenay and Fabienne Prieur and Ferrer, {Sandra Fert} and Isabelle Mortemousque and Saundra Buys and Mary Daly and Alexander Miron and Terry, {Mary Beth} and Hopper, {John L.} and John, {Esther M.} and Melissa Southey and David Goldgar and Singer, {Christian F.} and Anneliese Fink-Retter and Muy-Kheng Tea and Kaulich, {Daphne Geschwantler} and Hansen, {Thomas V. O.} and Nielsen, {Finn C.} and Barkardottir, {Rosa B.} and Mia Gaudet and Tomas Kirchhoff and Vijai Joseph and Ana Dutra-Clarke and Kenneth Offit and Marion Piedmonte and Judy Kirk and David Cohn and Jean Hurteau and John Byron and James Fiorica and Toland, {Amanda E.} and Marco Montagna and Cristina Oliani and Evgeny Imyanitov and Claudine Isaacs and Laima Tihomirova and Ignacio Blanco and Conxi Lazaro and Alex Teule and {Del Valle}, J. and Gayther, {Simon A.} and Kunle Odunsi and Jenny Gross and Karlan, {Beth Y.} and Edith Olah and Soo-Hwang Teo and Ganz, {Patricia A.} and Beattie, {Mary S.} and Dorfling, {Cecelia M.} and {van Rensburg}, {Elizabeth Jansen} and Orland Diez and Ava Kwong and Schmutzler, {Rita K.} and Barbara Wappenschmidt and Christoph Engel and Alfons Meindl and Nina Ditsch and Norbert Arnold and Simone Heidemann and Dieter Niederacher and Sabine Preisler-Adams and Dorothea Gadzicki and Raymonda Varon-Mateeva and Helmut Deissler and Andrea Gehrig and Christian Sutter and Karin Kast and Britta Fiebig and Dieter Schaefer and Trinidad Caldes and {de la Hoya}, Miguel and Heli Nevanlinna and Muranen, {Taru A.} and Bernard Lesperance and Spurdle, {Amanda B.} and Neuhausen, {Susan L.} and Ding, {Yuan C.} and Xianshu Wang and Zachary Fredericksen and Pankratz, {Vernon S.} and Lindor, {Noralane M.} and Paolo Peterlongo and Siranoush Manoukian and Bernard Peissel and Daniela Zaffaroni and Bernardo Bonanni and Loris Bernard and Riccardo Dolcetti and Laura Papi and Laura Ottini and Paolo Radice and Greene, {Mark H.} and Loud, {Jennifer T.} and Andrulis, {Irene L.} and Hilmi Ozcelik and Mulligan, {Anna Marie} and Gord Glendon and Mads Thomassen and Anne-Marie Gerdes and Jensen, {Uffe B.} and Anne-Bine Skytte and Kruse, {Torben A.} and Georgia Chenevix-Trench and Couch, {Fergus J.} and Jacques Simard and Easton, {Douglas F.}",
year = "2012",
doi = "10.1186/bcr3121",
language = "English",
volume = "14",
journal = "Breast Cancer Research",
issn = "1465-5411",
publisher = "BioMed Central (BMC)",
number = "1",