Advanced

Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers

Antoniou, Antonis C.; Sinilnikova, Olga M.; McGuffog, Lesley; Healey, Sue; Nevanlinna, Heli; Heikkinen, Tuomas; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan and Chen, Xiaoqing, et al. (2009) In Human Molecular Genetics 18(22). p.4442-4456
Abstract
Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated... (More)
Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Population, Genetics, Genetic Variation, Genetic Predisposition to Disease, Follow-Up Studies, Female, Pair 8, Pair 2, Human, Chromosomes, Breast Neoplasms, BRCA2 Protein, BRCA1 Protein, 80 and over, Adult, Aged, Genome-Wide Association Study, Heterozygote, Humans, Microfilament Proteins, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Young Adult
in
Human Molecular Genetics
volume
18
issue
22
pages
4442 - 4456
publisher
Oxford University Press
external identifiers
  • wos:000271107300019
  • scopus:71049194443
ISSN
0964-6906
DOI
10.1093/hmg/ddp372
language
English
LU publication?
yes
id
e7129d54-d628-4331-a733-d905dd821c3f (old id 1505398)
alternative location
http://dx.doi.org/10.1093/hmg/ddp372
http://www.ncbi.nlm.nih.gov/pubmed/19656774
date added to LUP
2009-11-24 11:15:34
date last changed
2017-05-21 03:34:47
@article{e7129d54-d628-4331-a733-d905dd821c3f,
  abstract     = {Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.},
  author       = {Antoniou, Antonis C. and Sinilnikova, Olga M. and McGuffog, Lesley and Healey, Sue and Nevanlinna, Heli and Heikkinen, Tuomas and Simard, Jacques and Spurdle, Amanda B. and Beesley, Jonathan and Chen, Xiaoqing and Neuhausen, Susan L. and Ding, Yuan C. and Couch, Fergus J. and Wang, Xianshu and Fredericksen, Zachary and Peterlongo, Paolo and Peissel, Bernard and Bonanni, Bernardo and Viel, Alessandra and Bernard, Loris and Radice, Paolo and Szabo, Csilla I. and Foretova, Lenka and Zikan, Michal and Claes, Kathleen and Greene, Mark H. and Mai, Phuong L. and Rennert, Gad and Lejbkowicz, Flavio and Andrulis, Irene L. and Ozcelik, Hilmi and Glendon, Gord and Gerdes, Anne-Marie and Thomassen, Mads and Sunde, Lone and Caligo, Maria A. and Laitman, Yael and Kontorovich, Tair and Cohen, Shimrit and Kaufman, Bella and Efrat, [unknown] and Baruch, Ruth Gershoni and Friedman, Eitan and Harbst, Katja and Barbany-Bustinza, Gisela and Rantala, Johanna and Ehrencrona, Hans and Karlsson, Per and Domchek, Susan M. and Nathanson, Katherine L. and Osorio, Ana and Blanco, Ignacio and Lasa, Adriana and Benitez, Javier and Hamann, Ute and Hogervorst, Frans B. L. and Rookus, Matti A. and Collee, J. Margriet and Devilee, Peter and Ligtenberg, Marjolijn J. and van der Luijt, Rob B. and Aalfs, Cora M. and Waisfisz, Quinten and Wijnen, Juul and van Roozendaal, Cornelis E. P. and Peock, Susan and Cook, Margaret and Frost, Debra and Oliver, Clare and Platte, Radka and Evans, D. Gareth and Lalloo, Fiona and Eeles, Rosalind and Izatt, Louise and Davidson, Rosemarie and Chu, Carol and Eccles, Diana and Cole, Trevor and Hodgson, Shirley and Godwin, Andrew K. and Stoppa-Lyonnet, Dominique and Buecher, Bruno and Leone, Melanie and Bressac-de Paillerets, Brigitte and Remenieras, Audrey and Caron, Olivier and Lenoir, Gilbert M. and Sevenet, Nicolas and Longy, Michel and Ferrer, Sandra Fert and Prieur, Fabienne and Goldgar, David and Miron, Alexander and John, Esther M. and Buys, Saundra S. and Daly, Mary B. and Hopper, John L. and Terry, Mary Beth and Yassin, Yosuf and Singer, Christian and Gschwantler-Kaulich, Daphne and Staudigl, Christine and Hansen, Thomas V. O. and Barkardottir, Rosa Bjork and Kirchhoff, Tomas and Pal, Prodipto and Kosarin, Kristi and Offit, Kenneth and Piedmonte, Marion and Rodriguez, Gustavo C. and Wakeley, Katie and Boggess, John F. and Basil, Jack and Schwartz, Peter E. and Blank, Stephanie V. and Toland, Amanda E. and Montagna, Marco and Casella, Cinzia and Imyanitov, Evgeny N. and Allavena, Anna and Schmutzler, Rita K. and Versmold, Beatrix and Engel, Christoph and Meindl, Alfons and Ditsch, Nina and Arnold, Norbert and Niederacher, Dieter and Deissler, Helmut and Fiebig, Britta and Suttner, Christian and Schoenbuchner, Ines and Gadzicki, Dorothea and Caldes, Trinidad and de la Hoya, Miguel and Pooley, Karen A. and Easton, Douglas F. and Chenevix-Trench, Georgia},
  issn         = {0964-6906},
  keyword      = {Population,Genetics,Genetic Variation,Genetic Predisposition to Disease,Follow-Up Studies,Female,Pair 8,Pair 2,Human,Chromosomes,Breast Neoplasms,BRCA2 Protein,BRCA1 Protein,80 and over,Adult,Aged,Genome-Wide Association Study,Heterozygote,Humans,Microfilament Proteins,Middle Aged,Mutation,Polymorphism,Single Nucleotide,Young Adult},
  language     = {eng},
  number       = {22},
  pages        = {4442--4456},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers},
  url          = {http://dx.doi.org/10.1093/hmg/ddp372},
  volume       = {18},
  year         = {2009},
}