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Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

Osorio, A.; Milne, R. L.; Alonso, R.; Pita, G.; Peterlongo, P.; Teule, A.; Nathanson, K. L.; Domchek, S. M.; Rebbeck, T. and Lasa, A., et al. (2011) In British Journal of Cancer 104(8). p.1356-1361
Abstract
BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS:... (More)
BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers. British Journal of Cancer (2011) 104, 1356-1361. doi:10.1038/bjc.2011.91 www.bjcancer.com Published online 22 March 2011 (C) 2011 Cancer Research UK (Less)
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Genetic Predisposition to Disease, BRCA2, BRCA1, Genes, Focus Groups, Female, Genetic, Epistasis, DNA-Binding Proteins, Carcinoma, Breast Neoplasms, 80 and over, Aged, Adolescent, Adult, Heterozygote, Humans, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Young Adult
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British Journal of Cancer
volume
104
issue
8
pages
1356 - 1361
publisher
Nature Publishing Group
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  • wos:000289458400017
  • scopus:79954440124
ISSN
1532-1827
DOI
10.1038/bjc.2011.91
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English
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yes
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fd3db35e-17d2-47ed-95a6-e81cdffe31d1 (old id 1965913)
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http://dx.doi.org/10.1038/bjc.2011.91
http://www.ncbi.nlm.nih.gov/pubmed/21427728
date added to LUP
2011-06-01 10:50:28
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2017-01-01 03:26:28
@article{fd3db35e-17d2-47ed-95a6-e81cdffe31d1,
  abstract     = {BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C&gt;T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P&lt;0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers. British Journal of Cancer (2011) 104, 1356-1361. doi:10.1038/bjc.2011.91 www.bjcancer.com Published online 22 March 2011 (C) 2011 Cancer Research UK},
  author       = {Osorio, A. and Milne, R. L. and Alonso, R. and Pita, G. and Peterlongo, P. and Teule, A. and Nathanson, K. L. and Domchek, S. M. and Rebbeck, T. and Lasa, A. and Konstantopoulou, I. and Hogervorst, F. B. and Verhoef, S. and van Dooren, M. F. and Jager, A. and Ausems, M. G. E. M. and Aalfs, C. M. and van Asperen, C. J. and Vreeswijk, M. and Waisfisz, Q. and Van Roozendaal, C. E. and Ligtenberg, M. J. and Easton, D. F. and Peock, S. and Cook, M. and Oliver, C. T. and Frost, D. and Curzon, B. and Evans, D. G. and Lalloo, F. and Eeles, R. and Izatt, L. and Davidson, R. and Adlard, J. and Eccles, D. and Ong, K-R and Douglas, F. and Downing, S. and Brewer, C. and Walker, L. and Nevanlinna, H. and Aittomaki, K. and Couch, F. J. and Fredericksen, Z. and Lindor, N. M. and Godwin, A. and Isaacs, C. and Caligo, M. A. and Loman, Niklas and Jernström, Helena and Barbany-Bustinza, G. and Liljegren, A. and Ehrencrona, Hans and Stenmark-Askmalm, M. and Feliubadalo, L. and Manoukian, S. and Peissel, B. and Zaffaroni, D. and Bonanni, B. and Fortuzzi, S. and Johannsson, O. T. and Chenevix-Trench, G. and Chen, X-C and Beesley, J. and Spurdle, A. B. and Sinilnikova, O. M. and Healey, S. and McGuffog, L. and Antoniou, A. C. and Brunet, J. and Radice, P. and Benitez, J.},
  issn         = {1532-1827},
  keyword      = {Genetic Predisposition to Disease,BRCA2,BRCA1,Genes,Focus Groups,Female,Genetic,Epistasis,DNA-Binding Proteins,Carcinoma,Breast Neoplasms,80 and over,Aged,Adolescent,Adult,Heterozygote,Humans,Middle Aged,Phenotype,Polymorphism,Single Nucleotide,Young Adult},
  language     = {eng},
  number       = {8},
  pages        = {1356--1361},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2},
  url          = {http://dx.doi.org/10.1038/bjc.2011.91},
  volume       = {104},
  year         = {2011},
}