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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

Antoniou, Antonis C.; Wang, Xianshu; Fredericksen, Zachary S.; McGuffog, Lesley; Tarrell, Robert; Sinilnikova, Olga M.; Healey, Sue; Morrison, Jonathan; Kartsonaki, Christiana and Lesnick, Timothy, et al. (2010) In Nature Genetics 42(10). p.885-892
Abstract
Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800... (More)
Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)). (Less)
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Mutation, Humans, Genotype, Genetic Predisposition to Disease, Female, Pair 19, Human, Chromosomes, Case-Control Studies, Breast Neoplasms, Adult, BRCA1 Protein, Polymorphism, Single Nucleotide, Receptor, erbB-2, Receptors, Estrogen, Progesterone
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Nature Genetics
volume
42
issue
10
pages
885 - 892
publisher
Nature Publishing Group
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  • wos:000282276600020
  • scopus:77957568513
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1546-1718
DOI
10.1038/ng.669
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English
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yes
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e3b8ea03-2f13-4a39-ab70-4acd450f7cad (old id 1694599)
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http://dx.doi.org/10.1038/ng.669
http://www.ncbi.nlm.nih.gov/pubmed/20852631
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2010-10-26 10:18:20
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2018-06-24 04:20:46
@article{e3b8ea03-2f13-4a39-ab70-4acd450f7cad,
  abstract     = {Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).},
  author       = {Antoniou, Antonis C. and Wang, Xianshu and Fredericksen, Zachary S. and McGuffog, Lesley and Tarrell, Robert and Sinilnikova, Olga M. and Healey, Sue and Morrison, Jonathan and Kartsonaki, Christiana and Lesnick, Timothy and Ghoussaini, Maya and Barrowdale, Daniel and Peock, Susan and Cook, Margaret and Oliver, Clare and Frost, Debra and Eccles, Diana and Evans, D. Gareth and Eeles, Ros and Izatt, Louise and Chu, Carol and Douglas, Fiona and Paterson, Joan and Stoppa-Lyonnet, Dominique and Houdayer, Claude and Mazoyer, Sylvie and Giraud, Sophie and Lasset, Christine and Remenieras, Audrey and Caron, Olivier and Hardouin, Agnes and Berthet, Pascaline and Hogervorst, Frans B. L. and Rookus, Matti A. and Jager, Agnes and van den Ouweland, Ans and Hoogerbrugge, Nicoline and van der Luijt, Rob B. and Meijers-Heijboer, Hanne and Garcia, Encarna B. Gomez and Devilee, Peter and Vreeswijk, Maaike P. G. and Lubinski, Jan and Jakubowska, Anna and Gronwald, Jacek and Huzarski, Tomasz and Byrski, Tomasz and Gorski, Bohdan and Cybulski, Cezary and Spurdle, Amanda B. and Holland, Helene and Goldgar, David E. and John, Esther M. and Hopper, John L. and Southey, Melissa and Buys, Saundra S. and Daly, Mary B. and Terry, Mary-Beth and Schmutzler, Rita K. and Wappenschmidt, Barbara and Engel, Christoph and Meindl, Alfons and Preisler-Adams, Sabine and Arnold, Norbert and Niederacher, Dieter and Sutter, Christian and Domchek, Susan M. and Nathanson, Katherine L. and Rebbeck, Timothy and Blum, Joanne L. and Piedmonte, Marion and Rodriguez, Gustavo C. and Wakeley, Katie and Boggess, John F. and Basil, Jack and Blank, Stephanie V. and Friedman, Eitan and Kaufman, Bella and Laitman, Yael and Milgrom, Roni and Andrulis, Irene L. and Glendon, Gord and Ozcelik, Hilmi and Kirchhoff, Tomas and Vijai, Joseph and Gaudet, Mia M. and Altshuler, David and Guiducci, Candace and Loman, Niklas and Harbst, Katja and Rantala, Johanna and Ehrencrona, Hans and Gerdes, Anne-Marie and Thomassen, Mads and Sunde, Lone and Peterlongo, Paolo and Manoukian, Siranoush and Bonanni, Bernardo and Viel, Alessandra and Radice, Paolo and Caldes, Trinidad and de la Hoya, Miguel and Singer, Christian F. and Fink-Retter, Anneliese and Greene, Mark H. and Mai, Phuong L. and Loud, Jennifer T. and Guidugli, Lucia and Lindor, Noralane M. and Hansen, Thomas V. O. and Nielsen, Finn C. and Blanco, Ignacio and Lazaro, Conxi and Garber, Judy and Ramus, Susan J. and Gayther, Simon A. and Phelan, Catherine and Narod, Stephen and Szabo, Csilla I. and Benitez, Javier and Osorio, Ana and Nevanlinna, Heli and Heikkinen, Tuomas and Caligo, Maria A. and Beattie, Mary S. and Hamann, Ute and Godwin, Andrew K. and Montagna, Marco and Casella, Cinzia and Neuhausen, Susan L. and Karlan, Beth Y. and Tung, Nadine and Toland, Amanda E. and Weitzel, Jeffrey and Olopade, Olofunmilayo and Simard, Jacques and Soucy, Penny and Rubinstein, Wendy S. and Arason, Adalgeir and Rennert, Gad and Martin, Nicholas G. and Montgomery, Grant W. and Chang-Claude, Jenny and Flesch-Janys, Dieter and Brauch, Hiltrud and Severi, Gianluca and Baglietto, Laura and Cox, Angela and Cross, Simon S. and Miron, Penelope and Gerty, Sue M. and Tapper, William and Yannoukakos, Drakoulis and Fountzilas, George and Fasching, Peter A. and Beckmann, Matthias W. and Silva, Isabel dos Santos and Peto, Julian and Lambrechts, Diether and Paridaens, Robert and Ruediger, Thomas and Foersti, Asta and Winqvist, Robert and Pylkaes, Katri and Diasio, Robert B. and Lee, Adam M. and Eckel-Passow, Jeanette and Vachon, Celine and Blows, Fiona and Driver, Kristy and Dunning, Alison and Pharoah, Paul P. D. and Offit, Kenneth and Pankratz, V. Shane and Hakonarson, Hakon and Chenevix-Trench, Georgia and Easton, Douglas F. and Couch, Fergus J.},
  issn         = {1546-1718},
  keyword      = {Mutation,Humans,Genotype,Genetic Predisposition to Disease,Female,Pair 19,Human,Chromosomes,Case-Control Studies,Breast Neoplasms,Adult,BRCA1 Protein,Polymorphism,Single Nucleotide,Receptor,erbB-2,Receptors,Estrogen,Progesterone},
  language     = {eng},
  number       = {10},
  pages        = {885--892},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population},
  url          = {http://dx.doi.org/10.1038/ng.669},
  volume       = {42},
  year         = {2010},
}