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
Por:
Osorio, A, Milne, RL, Alonso, R, Pita, G, Peterlongo, P, Teule, A, Nathanson, KL, Domchek, SM, Rebbeck, T, Lasa, A, Konstantopoulou, I, Hogervorst, FB, Verhoef, S, van Dooren, MF, Jager, A, Ausems, MGEM, Aalfs, CM, van Asperen, CJ, Vreeswijk, M, Waisfisz, Q, Van Roozendaal, CE, Ligtenberg, MJ, Easton, DF, Peock, S, Cook, M, Oliver, CT, Frost, D, Curzon, B, Evans, DG, Lalloo, F, Eeles, R, Izatt, L, Davidson, R, Adlard, J, Eccles, D, Ong, KR, Douglas, F, Downing, S, Brewer, C, Walker, L, Nevanlinna, H, Aittomaki, K, Couch, FJ, Fredericksen, Z, Lindor, NM, Godwin, A, Isaacs, C, Caligo, MA, Loman, N, Jernstrom, H, Barbany-Bustinza, G, Liljegren, A, Ehrencrona, H, Stenmark-Askmalm, M, Feliubadalo, L, Manoukian, S, Peissel, B, Zaffaroni, D, Bonanni, B, Fortuzzi, S, Johannsson, OT, Chenevix-Trench, G, Chen, XC, Beesley, J, Spurdle, AB, Sinilnikova, OM, Healey, S, McGuffog, L, Antoniou, AC, Brunet, J, Radice, P, Benitez, J
Publicada:
12 abr 2011
Resumen:
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
Filiaciones:
Osorio, A:
Spanish Natl Canc Ctr, Human Genet Grp, Madrid 28029, Spain
Spanish Network Rare Dis CIBERER, Barcelona, Spain
Milne, RL:
Spanish Natl Canc Ctr, Genet & Mol Epidemiol Grp, Madrid 28029, Spain
Alonso, R:
Spanish Natl Canc Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid 28029, Spain
Pita, G:
Spanish Natl Canc Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid 28029, Spain
Peterlongo, P:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy
Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy
Teule, A:
Catalan Inst Oncol, Hereditary Canc Program, Girona, Catalonia, Spain
Nathanson, KL:
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Domchek, SM:
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Rebbeck, T:
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA
Lasa, A:
Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain
Konstantopoulou, I:
NCSR Demokritos, Mol Diagnost Lab IRRP, Aghia Paraskevi 15310, Greece
Hogervorst, FB:
Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands
Verhoef, S:
Netherlands Canc Inst, Dept Clin Genet, Amsterdam, Netherlands
van Dooren, MF:
Erasmus Univ, Dept Clin Genet, Med Ctr, Family Canc Clin, NL-3000 DR Rotterdam, Netherlands
Jager, A:
Erasmus Univ, Dept Med Oncol, Family Canc Clin, Med Ctr, Rotterdam, Netherlands
Ausems, MGEM:
Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands
Aalfs, CM:
Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands
van Asperen, CJ:
Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands
Vreeswijk, M:
Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands
Leiden Univ, Dept Toxicogenet, Med Ctr, Leiden, Netherlands
Waisfisz, Q:
Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands
Van Roozendaal, CE:
Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands
Ligtenberg, MJ:
Radboud Univ Nijmegen, Med Ctr, Dept Human Genet & Pathol, NL-6525 ED Nijmegen, Netherlands
Easton, DF:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England
Peock, S:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England
Cook, M:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England
Oliver, CT:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England
Frost, D:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England
Curzon, B:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB2 1TN, England
Evans, DG:
Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England
Lalloo, F:
Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England
Eeles, R:
Inst Canc Res & Royal Marsden NHS Fdn Trust, Oncogenet Team, London, England
Izatt, L:
Guys & St Thomas NHS Fdn Trust, London, England
Davidson, R:
Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland
Adlard, J:
Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England
Eccles, D:
Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England
Ong, KR:
Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England
Douglas, F:
Newcastle Upon Tyne Hosp NHS Trust, Inst Human Genet, Ctr Life, Newcastle Upon Tyne, Tyne & Wear, England
Downing, S:
Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England
Brewer, C:
Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England
Walker, L:
Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England
Nevanlinna, H:
Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland
Couch, FJ:
Mayo Clin, Dept Lab Med & Pathol, Rochester, MI USA
Mayo Clin, Dept Hlth Sci Res, Rochester, MI USA
Fredericksen, Z:
Mayo Clin, Dept Hlth Sci Res, Rochester, MI USA
Lindor, NM:
Mayo Clin, Dept Med Genet, Rochester, MI USA
Godwin, A:
Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Lawrence, KS 66045 USA
Isaacs, C:
MD Georgetown Univ, Washington, DC USA
Caligo, MA:
Univ & Univ Hosp Pisa, Dept Oncol, Div Pathol, Pisa, Italy
Loman, N:
Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden
Jernstrom, H:
Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden
Barbany-Bustinza, G:
Karolinska Univ Hosp, Dept Clin Genet, S-17176 Stockholm, Sweden
Liljegren, A:
Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden
Ehrencrona, H:
Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, S-75185 Uppsala, Sweden
Stenmark-Askmalm, M:
Linkoping Univ Hosp, Dept Oncol, Linkoping, Sweden
Feliubadalo, L:
Catalan Inst Oncol, Hereditary Canc Program, Girona, Catalonia, Spain
Manoukian, S:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy
Peissel, B:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy
Zaffaroni, D:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy
Bonanni, B:
Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy
Fortuzzi, S:
Cogentech, Consortium Genom Technol, Milan, Italy
Johannsson, OT:
Univ Iceland, Landspitali, Fac Med, Dept Oncol,Univ Hosp, Reykjavik, Iceland
Chenevix-Trench, G:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
Chen, XC:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
Beesley, J:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
Spurdle, AB:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
Sinilnikova, OM:
Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France
Univ Lyon, Ctr Leon Berard, Equipe Labellisee LIGUE 2008, CNRS UMR5201, Lyon, France
Healey, S:
Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia
McGuffog, L:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England
Antoniou, AC:
Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England
Brunet, J:
Catalan Inst Oncol, Hereditary Canc Program, Girona, Catalonia, Spain
Radice, P:
Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy
Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy
Benitez, J:
Spanish Natl Canc Ctr, Human Genet Grp, Madrid 28029, Spain
Spanish Network Rare Dis CIBERER, Barcelona, Spain
Spanish Natl Canc Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid 28029, Spain
Green Published, Hybrid Gold
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