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dc.contributor.authorOsorio, A
dc.contributor.authorMilne, R L
dc.contributor.authorAlonso, R
dc.contributor.authorPita, G
dc.contributor.authorPeterlongo, P
dc.contributor.authorTeulé, A
dc.contributor.authorNathanson, K L
dc.contributor.authorDomchek, S M
dc.contributor.authorRebbeck, T
dc.contributor.authorLasa, A
dc.contributor.authorKonstantopoulou, I
dc.contributor.authorHogervorst, F B
dc.contributor.authorVerhoef, S
dc.contributor.authorvan Dooren, M F
dc.contributor.authorJager, A
dc.contributor.authorAusems, M G E M
dc.contributor.authorAalfs, C M
dc.contributor.authorvan Asperen, C J
dc.contributor.authorVreeswijk, M
dc.contributor.authorWaisfisz, Q
dc.contributor.authorVan Roozendaal, C E
dc.contributor.authorLigtenberg, M J
dc.contributor.authorEaston, D F
dc.contributor.authorPeock, S
dc.contributor.authorCook, M
dc.contributor.authorOliver, C T
dc.contributor.authorFrost, D
dc.contributor.authorCurzon, B
dc.contributor.authorEvans, D G
dc.contributor.authorLalloo, F
dc.contributor.authorEeles, R
dc.contributor.authorIzatt, L
dc.contributor.authorDavidson, R
dc.contributor.authorAdlard, J
dc.contributor.authorEccles, D
dc.contributor.authorOng, K-r
dc.contributor.authorDouglas, F
dc.contributor.authorDowning, S
dc.contributor.authorBrewer, C
dc.contributor.authorWalker, L
dc.contributor.authorNevanlinna, H
dc.contributor.authorAittomäki, K
dc.contributor.authorCouch, F J
dc.contributor.authorFredericksen, Z
dc.contributor.authorLindor, N M
dc.contributor.authorGodwin, A
dc.contributor.authorIsaacs, C
dc.contributor.authorCaligo, M A
dc.contributor.authorLoman, N
dc.contributor.authorJernström, H
dc.contributor.authorBarbany-Bustinza, G
dc.contributor.authorLiljegren, A
dc.contributor.authorEhrencrona, H
dc.contributor.authorStenmark-Askmalm, M
dc.contributor.authorFeliubadaló, L
dc.contributor.authorManoukian, S
dc.contributor.authorPeissel, B
dc.contributor.authorZaffaroni, D
dc.contributor.authorBonanni, B
dc.contributor.authorFortuzzi, S
dc.contributor.authorJohannsson, O T
dc.contributor.authorChenevix-Trench, G
dc.contributor.authorChen, X-C
dc.contributor.authorBeesley, J
dc.contributor.authorSpurdle, A B
dc.contributor.authorSinilnikova, O M
dc.contributor.authorHealey, S
dc.contributor.authorMcGuffog, L
dc.contributor.authorAntoniou, A C
dc.contributor.authorBrunet, J
dc.contributor.authorRadice, P
dc.contributor.authorBenítez, J
dc.date.accessioned2012-06-05T14:36:53Z
dc.date.available2012-06-05T14:36:53Z
dc.date.issued2011-04-12
dc.date.submitted2012-06-05
dc.identifier.citationBr. J. Cancer 2011, 104(8):1356-61 Br. J. Canceren_GB
dc.identifier.issn1532-1827
dc.identifier.pmid21427728
dc.identifier.doi10.1038/bjc.2011.91
dc.identifier.urihttp://hdl.handle.net/2336/227575
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractBACKGROUND: 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.
dc.description.sponsorshipMutua Madrilena Foundations Ministry of Science FIS08-1120 European Community 223175 (HEALTH-F2-2009-223175) Fondazione Italiana per la Ricerca sul Cancro Associazione Italiana per la Ricerca sul Cancro 4017 Ministero della Salute RFPS-2006-3-340203 Ministero dell'Universitae Ricerca RBLAO3-BETH Fondazione IRCCS Istituto Nazionale Tumori NHMRC 145684 288704 454508 National Breast Cancer Foundation National Health and Medical Research Council Queensland Cancer Fund Cancer Councils of New South Wales, Victoria, Tasmania and South Australia Cancer Foundation of Western Australia National Institute of Health CA116167 CA122340 CA128978 Breast Cancer Research Foundation P50 CA116201 Komen Foundation for the Cure Institute for Tumors of Tuscany Breast Cancer Research Foundation MacDonald Family Foundation Dutch Cancer Society NKI1998-1854 NKI2004-3088 NKI2007-3756 Cancer Research UK C1287/A10118 C1287/A11990 C8197/A10123 C5047/A8385 NIHR Royal Marsden NHS Foundation Trusten_GB
dc.language.isoenen
dc.publisherNature Publishing Group on behalf of Cancer Research UKen_GB
dc.relation.urlhttp://dx.doi.org/10.1038/bjc.2011.91en_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078599/?tool=pubmeden_GB
dc.rightsArchived with thanks to British journal of canceren_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshBreast Neoplasmsen_GB
dc.subject.meshCarcinomaen_GB
dc.subject.meshDNA-Binding Proteinsen_GB
dc.subject.meshEpistasis, Geneticen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFocus Groupsen_GB
dc.subject.meshGenes, BRCA1en_GB
dc.subject.meshGenes, BRCA2en_GB
dc.subject.meshGenetic Predisposition to Diseaseen_GB
dc.subject.meshHeterozygoteen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshPhenotypeen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshYoung Adulten_GB
dc.titleEvaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2.en
dc.typeArticleen
dc.contributor.departmentHuman Genetics Group, Spanish National Cancer Centre, C/Melchor Fernández Almagro 3, 28029 Madrid, Spain. aosorio@cnio.esen_GB
dc.identifier.journalBritish journal of canceren_GB
html.description.abstractBACKGROUND: 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.


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