DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers

2.50
Hdl Handle:
http://hdl.handle.net/11287/593865
Title:
DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers
Authors:
Osorio, A.; Milne, R. L.; Kuchenbaecker, K.; Vaclova, T.; Pita, G.; Alonso, R.; Peterlongo, P.; Blanco, I.; de la Hoya, M.; Duran, M.; Diez, O.; Ramon, Y. Cajal T.; Konstantopoulou, I.; Martinez-Bouzas, C.; Andres Conejero, R.; Soucy, P.; McGuffog, L.; Barrowdale, D.; Lee, A.; Swe, Brca; Arver, B.; Rantala, J.; Loman, N.; Ehrencrona, H.; Olopade, O. I.; Beattie, M. S.; Domchek, S. M.; Nathanson, K.; Rebbeck, T. R.; Arun, B. K.; Karlan, B. Y.; Walsh, C.; Lester, J.; John, E. M.; Whittemore, A. S.; Daly, M.; Southey, M.; Hopper, J.; Terry, M. B.; Buys, S. S.; Janavicius, R.; Dorfling, C. M.; van Rensburg, E. J.; Steele, L.; Neuhausen, S. L.; Ding, Y. C.; Hansen, T. V.; Jonson, L.; Ejlertsen, B.; Gerdes, A. M.; Infante, M.; Herraez, B.; Moreno, L. T.; Weitzel, J. N.; Herzog, J.; Weeman, K.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Scuvera, G.; Bonanni, B.; Mariette, F.; Volorio, S.; Viel, A.; Varesco, L.; Papi, L.; Ottini, L.; Tibiletti, M. G.; Radice, P.; Yannoukakos, D.; Garber, J.; Ellis, S.; Frost, D.; Platte, R.; Fineberg, E.; Evans, G.; Lalloo, F.; Izatt, L.; Eeles, R.; Adlard, J.; Davidson, R.; Cole, T.; Eccles, D.; Cook, J.; Hodgson, S.; Brewer, Carole; Tischkowitz, M.; Douglas, F.; Porteous, M.; Side, L.; Walker, L.; Morrison, P.; Donaldson, A.; Kennedy, J.; Foo, C.; Godwin, A. K.; Schmutzler, R. K.; Wappenschmidt, B.; Rhiem, K.; Engel, C.; Meindl, A.; Ditsch, N.; Arnold, N.; Plendl, H. J.; Niederacher, D.; Sutter, C.; Wang-Gohrke, S.; Steinemann, D.; Preisler-Adams, S.; Kast, K.; Varon-Mateeva, R.; Gehrig, A.; Stoppa-Lyonnet, D.; Sinilnikova, O. M.; Mazoyer, S.; Damiola, F.; Poppe, B.; Claes, K.; Piedmonte, M.; Tucker, K.; Backes, F.; Rodriguez, G.; Brewster, W.; Wakeley, K.; Rutherford, T.; Caldes, T.; Nevanlinna, H.; Aittomaki, K.; Rookus, M. A.; van Os, T. A.; van der Kolk, L.; de Lange, J. L.; Meijers-Heijboer, H. E.; van der Hout, A. H.; van Asperen, C. J.; Gomez Garcia, E. B.; Hoogerbrugge, N.; Collee, J. M.; van Deurzen, C. H.; van der Luijt, R. B.; Devilee, P.; Hebon,; Olah, E.; Lazaro, C.; Teule, A.; Menendez, M.; Jakubowska, A.; Cybulski, C.; Gronwald, J.; Lubinski, J.; Durda, K.; Jaworska-Bieniek, K.; Johannsson, O. T.; Maugard, C.; Montagna, M.; Tognazzo, S.; Teixeira, M. R.; Healey, S.; Investigators, K.; Olswold, C.; Guidugli, L.; Lindor, N.; Slager, S.; Szabo, C. I.; Vijai, J.; Robson, M.; Kauff, N.; Zhang, L.; Rau-Murthy, R.; Fink-Retter, A.; Singer, C. F.; Rappaport, C.; Geschwantler Kaulich, D.; Pfeiler, G.; Tea, M. K.; Berger, A.; Phelan, C. M.; Greene, M. H.; Mai, P. L.; Lejbkowicz, F.; Andrulis, I.; Mulligan, A. M.; Glendon, G.; Toland, A. E.; Bojesen, A.; Pedersen, I. S.; Sunde, L.; Thomassen, M.; Kruse, T. A.; Jensen, U. B.; Friedman, E.; Laitman, Y.; Shimon, S. P.; Simard, J.; Easton, D. F.; Offit, K.; Couch, F. J.; Chenevix-Trench, G.; Antoniou, A. C.; Benitez, J.
Abstract:
Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 x 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 x 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
Citation:
PLoS Genet. 2014 Apr;10(4):e1004256.
Publisher:
PLoS
Journal:
PLoS genetics
Issue Date:
1-Apr-2014
URI:
http://hdl.handle.net/11287/593865
DOI:
10.1371/journal.pgen.1004256
PubMed ID:
24698998
Additional Links:
http://dx.plos.org/10.1371/journal.pgen.1004256
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
Language:
eng
ISSN:
1553-7404
Appears in Collections:
2014 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorOsorio, A.en
dc.contributor.authorMilne, R. L.en
dc.contributor.authorKuchenbaecker, K.en
dc.contributor.authorVaclova, T.en
dc.contributor.authorPita, G.en
dc.contributor.authorAlonso, R.en
dc.contributor.authorPeterlongo, P.en
dc.contributor.authorBlanco, I.en
dc.contributor.authorde la Hoya, M.en
dc.contributor.authorDuran, M.en
dc.contributor.authorDiez, O.en
dc.contributor.authorRamon, Y. Cajal T.en
dc.contributor.authorKonstantopoulou, I.en
dc.contributor.authorMartinez-Bouzas, C.en
dc.contributor.authorAndres Conejero, R.en
dc.contributor.authorSoucy, P.en
dc.contributor.authorMcGuffog, L.en
dc.contributor.authorBarrowdale, D.en
dc.contributor.authorLee, A.en
dc.contributor.authorSwe, Brcaen
dc.contributor.authorArver, B.en
dc.contributor.authorRantala, J.en
dc.contributor.authorLoman, N.en
dc.contributor.authorEhrencrona, H.en
dc.contributor.authorOlopade, O. I.en
dc.contributor.authorBeattie, M. S.en
dc.contributor.authorDomchek, S. M.en
dc.contributor.authorNathanson, K.en
dc.contributor.authorRebbeck, T. R.en
dc.contributor.authorArun, B. K.en
dc.contributor.authorKarlan, B. Y.en
dc.contributor.authorWalsh, C.en
dc.contributor.authorLester, J.en
dc.contributor.authorJohn, E. M.en
dc.contributor.authorWhittemore, A. S.en
dc.contributor.authorDaly, M.en
dc.contributor.authorSouthey, M.en
dc.contributor.authorHopper, J.en
dc.contributor.authorTerry, M. B.en
dc.contributor.authorBuys, S. S.en
dc.contributor.authorJanavicius, R.en
dc.contributor.authorDorfling, C. M.en
dc.contributor.authorvan Rensburg, E. J.en
dc.contributor.authorSteele, L.en
dc.contributor.authorNeuhausen, S. L.en
dc.contributor.authorDing, Y. C.en
dc.contributor.authorHansen, T. V.en
dc.contributor.authorJonson, L.en
dc.contributor.authorEjlertsen, B.en
dc.contributor.authorGerdes, A. M.en
dc.contributor.authorInfante, M.en
dc.contributor.authorHerraez, B.en
dc.contributor.authorMoreno, L. T.en
dc.contributor.authorWeitzel, J. N.en
dc.contributor.authorHerzog, J.en
dc.contributor.authorWeeman, K.en
dc.contributor.authorManoukian, S.en
dc.contributor.authorPeissel, B.en
dc.contributor.authorZaffaroni, D.en
dc.contributor.authorScuvera, G.en
dc.contributor.authorBonanni, B.en
dc.contributor.authorMariette, F.en
dc.contributor.authorVolorio, S.en
dc.contributor.authorViel, A.en
dc.contributor.authorVaresco, L.en
dc.contributor.authorPapi, L.en
dc.contributor.authorOttini, L.en
dc.contributor.authorTibiletti, M. G.en
dc.contributor.authorRadice, P.en
dc.contributor.authorYannoukakos, D.en
dc.contributor.authorGarber, J.en
dc.contributor.authorEllis, S.en
dc.contributor.authorFrost, D.en
dc.contributor.authorPlatte, R.en
dc.contributor.authorFineberg, E.en
dc.contributor.authorEvans, G.en
dc.contributor.authorLalloo, F.en
dc.contributor.authorIzatt, L.en
dc.contributor.authorEeles, R.en
dc.contributor.authorAdlard, J.en
dc.contributor.authorDavidson, R.en
dc.contributor.authorCole, T.en
dc.contributor.authorEccles, D.en
dc.contributor.authorCook, J.en
dc.contributor.authorHodgson, S.en
dc.contributor.authorBrewer, Caroleen
dc.contributor.authorTischkowitz, M.en
dc.contributor.authorDouglas, F.en
dc.contributor.authorPorteous, M.en
dc.contributor.authorSide, L.en
dc.contributor.authorWalker, L.en
dc.contributor.authorMorrison, P.en
dc.contributor.authorDonaldson, A.en
dc.contributor.authorKennedy, J.en
dc.contributor.authorFoo, C.en
dc.contributor.authorGodwin, A. K.en
dc.contributor.authorSchmutzler, R. K.en
dc.contributor.authorWappenschmidt, B.en
dc.contributor.authorRhiem, K.en
dc.contributor.authorEngel, C.en
dc.contributor.authorMeindl, A.en
dc.contributor.authorDitsch, N.en
dc.contributor.authorArnold, N.en
dc.contributor.authorPlendl, H. J.en
dc.contributor.authorNiederacher, D.en
dc.contributor.authorSutter, C.en
dc.contributor.authorWang-Gohrke, S.en
dc.contributor.authorSteinemann, D.en
dc.contributor.authorPreisler-Adams, S.en
dc.contributor.authorKast, K.en
dc.contributor.authorVaron-Mateeva, R.en
dc.contributor.authorGehrig, A.en
dc.contributor.authorStoppa-Lyonnet, D.en
dc.contributor.authorSinilnikova, O. M.en
dc.contributor.authorMazoyer, S.en
dc.contributor.authorDamiola, F.en
dc.contributor.authorPoppe, B.en
dc.contributor.authorClaes, K.en
dc.contributor.authorPiedmonte, M.en
dc.contributor.authorTucker, K.en
dc.contributor.authorBackes, F.en
dc.contributor.authorRodriguez, G.en
dc.contributor.authorBrewster, W.en
dc.contributor.authorWakeley, K.en
dc.contributor.authorRutherford, T.en
dc.contributor.authorCaldes, T.en
dc.contributor.authorNevanlinna, H.en
dc.contributor.authorAittomaki, K.en
dc.contributor.authorRookus, M. A.en
dc.contributor.authorvan Os, T. A.en
dc.contributor.authorvan der Kolk, L.en
dc.contributor.authorde Lange, J. L.en
dc.contributor.authorMeijers-Heijboer, H. E.en
dc.contributor.authorvan der Hout, A. H.en
dc.contributor.authorvan Asperen, C. J.en
dc.contributor.authorGomez Garcia, E. B.en
dc.contributor.authorHoogerbrugge, N.en
dc.contributor.authorCollee, J. M.en
dc.contributor.authorvan Deurzen, C. H.en
dc.contributor.authorvan der Luijt, R. B.en
dc.contributor.authorDevilee, P.en
dc.contributor.authorHebon,en
dc.contributor.authorOlah, E.en
dc.contributor.authorLazaro, C.en
dc.contributor.authorTeule, A.en
dc.contributor.authorMenendez, M.en
dc.contributor.authorJakubowska, A.en
dc.contributor.authorCybulski, C.en
dc.contributor.authorGronwald, J.en
dc.contributor.authorLubinski, J.en
dc.contributor.authorDurda, K.en
dc.contributor.authorJaworska-Bieniek, K.en
dc.contributor.authorJohannsson, O. T.en
dc.contributor.authorMaugard, C.en
dc.contributor.authorMontagna, M.en
dc.contributor.authorTognazzo, S.en
dc.contributor.authorTeixeira, M. R.en
dc.contributor.authorHealey, S.en
dc.contributor.authorInvestigators, K.en
dc.contributor.authorOlswold, C.en
dc.contributor.authorGuidugli, L.en
dc.contributor.authorLindor, N.en
dc.contributor.authorSlager, S.en
dc.contributor.authorSzabo, C. I.en
dc.contributor.authorVijai, J.en
dc.contributor.authorRobson, M.en
dc.contributor.authorKauff, N.en
dc.contributor.authorZhang, L.en
dc.contributor.authorRau-Murthy, R.en
dc.contributor.authorFink-Retter, A.en
dc.contributor.authorSinger, C. F.en
dc.contributor.authorRappaport, C.en
dc.contributor.authorGeschwantler Kaulich, D.en
dc.contributor.authorPfeiler, G.en
dc.contributor.authorTea, M. K.en
dc.contributor.authorBerger, A.en
dc.contributor.authorPhelan, C. M.en
dc.contributor.authorGreene, M. H.en
dc.contributor.authorMai, P. L.en
dc.contributor.authorLejbkowicz, F.en
dc.contributor.authorAndrulis, I.en
dc.contributor.authorMulligan, A. M.en
dc.contributor.authorGlendon, G.en
dc.contributor.authorToland, A. E.en
dc.contributor.authorBojesen, A.en
dc.contributor.authorPedersen, I. S.en
dc.contributor.authorSunde, L.en
dc.contributor.authorThomassen, M.en
dc.contributor.authorKruse, T. A.en
dc.contributor.authorJensen, U. B.en
dc.contributor.authorFriedman, E.en
dc.contributor.authorLaitman, Y.en
dc.contributor.authorShimon, S. P.en
dc.contributor.authorSimard, J.en
dc.contributor.authorEaston, D. F.en
dc.contributor.authorOffit, K.en
dc.contributor.authorCouch, F. J.en
dc.contributor.authorChenevix-Trench, G.en
dc.contributor.authorAntoniou, A. C.en
dc.contributor.authorBenitez, J.en
dc.date.accessioned2016-01-19T12:35:58Zen
dc.date.available2016-01-19T12:35:58Zen
dc.date.issued2014-04-01en
dc.identifier.citationPLoS Genet. 2014 Apr;10(4):e1004256.en
dc.identifier.issn1553-7404en
dc.identifier.pmid24698998en
dc.identifier.doi10.1371/journal.pgen.1004256en
dc.identifier.urihttp://hdl.handle.net/11287/593865en
dc.description.abstractSingle Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 x 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 x 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.en
dc.language.isoengen
dc.publisherPLoSen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pgen.1004256en
dc.titleDNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriersen
dc.typeJournal Articleen
dc.typeResearch Support, N.I.H., Extramuralen
dc.typeResearch Support, N.I.H., Intramuralen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.typeResearch Support, U.S. Gov't, P.H.S.en
dc.identifier.journalPLoS geneticsen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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