Barrierefreiheit    Kontakt MedUni Wien    Intranet    MedUni Wien - Shop    Universitätsbibliothek    Universitätsklinikum AKH Wien  
 
 
 
 
 


    PLoS genetics. 2014 Apr 3. doi: 10.1371/journal.pgen.1004256. pii: PGENETICS-D-13-02923. pmc: PMC3974638
    DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.
    Osorio A1,  Milne RL2,  Kuchenbaecker K3,  Vaclová T4,  Pita G5,  Alonso R6,  Peterlongo P7,  Blanco I8,  de la Hoya M9,  Duran M10,  Díez O11,  Ramón Y Cajal T12,  Konstantopoulou I13,  Martínez-Bouzas C14,  Andrés Conejero R15,  Soucy P16,  McGuffog L17,  Barrowdale D18,  Lee A19,  Swe-Brca20,  Arver B21,  Rantala J22,  Loman N23,  Ehrencrona H24,  Olopade OI25,  Beattie MS26,  Domchek SM27,  Nathanson K28,  Rebbeck TR29,  Arun BK30,  Karlan BY31,  Walsh C32,  Lester J33,  John EM34,  Whittemore AS35,  Daly MB36,  Southey M37,  Hopper J38,  Terry MB39,  Buys SS40,  Janavicius R41,  Dorfling CM42,  van Rensburg EJ43,  Steele L44,  Neuhausen SL45,  Ding YC46,  Hansen TV47,  Jønson L48,  Ejlertsen B49,  Gerdes AM50,  Infante M51,  Herráez B52,  Moreno LT53,  Weitzel JN54,  Herzog J55,  Weeman K56,  Manoukian S57,  Peissel B58,  Zaffaroni D59,  Scuvera G60,  Bonanni B61,  Mariette F62,  Volorio S63,  Viel A64,  Varesco L65,  Papi L66,  Ottini L67,  Tibiletti MG68,  Radice P69,  Yannoukakos D70,  Garber J71,  Ellis S72,  Frost D73,  Platte R74,  Fineberg E75,  Evans G76,  Lalloo F77,  Izatt L78,  Eeles R79,  Adlard J80,  Davidson R81,  Cole T82,  Eccles D83,  Cook J84,  Hodgson S85,  Brewer C86,  Tischkowitz M87,  Douglas F88,  Porteous M89,  Side L90,  Walker L91,  Morrison P92,  Donaldson A93,  Kennedy J94,  Foo C95,  Godwin AK96,  Schmutzler RK97,  Wappenschmidt B98,  Rhiem K99,  Engel C100,  Meindl A101,  Ditsch N102,  Arnold N103,  Plendl HJ104,  Niederacher D105,  Sutter C106,  Wang-Gohrke S107,  Steinemann D108,  Preisler-Adams S109,  Kast K110,  Varon-Mateeva R111,  Gehrig A112,  Stoppa-Lyonnet D113,  Sinilnikova OM114,  Mazoyer S115,  Damiola F116,  Poppe B117,  Claes K118,  Piedmonte M119,  Tucker K120,  Backes F121,  Rodríguez G122,  Brewster W123,  Wakeley K124,  Rutherford T125,  Caldés T126,  Nevanlinna H127,  Aittomäki K128,  Rookus MA129,  van Os TA130,  van der Kolk L131,  de Lange JL132,  Meijers-Heijboer HE133,  van der Hout AH134,  van Asperen CJ135,  Gómez Garcia EB136,  Hoogerbrugge N137,  Collée JM138,  van Deurzen CH139,  van der Luijt RB140,  Devilee P141,  Hebon142,  Olah E143,  Lázaro C144,  Teulé A145,  Menéndez M146,  Jakubowska A147,  Cybulski C148,  Gronwald J149,  Lubinski J150,  Durda K151,  Jaworska-Bieniek K152,  Johannsson OT153,  Maugard C154,  Montagna M155,  Tognazzo S156,  Teixeira MR157,  Healey S158,  Investigators K159,  Olswold C160,  Guidugli L161,  Lindor N162,  Slager S163,  Szabo CI164,  Vijai J165,  Robson M166,  Kauff N167,  Zhang L168,  Rau-Murthy R169,  Fink-Retter A170,  Singer CF171,  Rappaport C172,  Geschwantler Kaulich D173,  Pfeiler G174,  Tea MK175,  Berger A176,  Phelan CM177,  Greene MH178,  Mai PL179,  Lejbkowicz F180,  Andrulis I181,  Mulligan AM182,  Glendon G183,  Toland AE184,  Bojesen A185,  Pedersen IS186,  Sunde L187,  Thomassen M188,  Kruse TA189,  Jensen UB190,  Friedman E191,  Laitman Y192,  Shimon SP193,  Simard J194,  Easton DF195,  Offit K196,  Couch FJ197,  Chenevix-Trench G198,  Antoniou AC199,  Benitez J200
    Author information
    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 × 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 × 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.


    Publikations ID: 24698998
    Quelle: öffnen
     
    Drucken
     
    ccc_logo_en.gif
    ccc_logo_en.gif
    ccc_logo_en.gif

    Schnellinfo

     
     

    Featured

     
     
     
     
     
     
     
     
     
     
     
     
     
    © MedUni Wien |
     Impressum | Nutzungsbedingungen | Kontakt