DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Creators: name: Osario, Ana
name: Milne, Roger L.
name: Kuchenbaecker, Karoline
name: Vaclova, Tereza
name: Pita, Guillermo
name: Alonso, Rosario
name: Peterlongo, Paolo
name: Blanco, Ignacio
name: De La Hoya, Miguel
name: Duran, Mercedes
name: Diez, Orland
name: Ramon Y Cajal, Teresa
name: Konstantopoulou, Irene
name: Martinez-Bouzas, Cristina
name: Soucy, Penny
name: Conejero, Raquel Andres
name: McGuffog, Lesley
name: Barrowdale, Daniel
name: Lee, Andrew
name: Arver, Brita
name: Rantala, Johanna
name: Loman, Niklas
name: Ehrencrona, Hans
name: Beattie, Mary S.
name: Olopade, Olufunmilayo I.
name: Domchek, Susan M.
name: Nathanson, Katherine
name: Rebbeck, Timothy R.
name: Arun, Banu K.
name: Karlan, Beth Y.
name: Walsh, Christine
name: Lester, Jenny
name: John, Esther M.
name: Whittemore, Alice S.
name: Daly, Mary B.
name: Southey, Melissa
name: Hopper, John
name: Terry, Mary Beth
name: Buys, Saundra S.
name: Janavicius, Ramunas
name: Dorfling, Cecilia M.
name: Van Rensburg, Elizabeth J.
name: Steele, Linda
name: Neuhausen, Susan L.
name: Ding, Yuan Chun
name: Hansen, Thomas V. O.
name: Jønson, Lars
name: Ejlertsen, Bent
name: Gerdes, Anne-Marie
name: Infante, Mar
name: Herraez, Belen
name: Moreno, Leticia Thais
name: Weitzel, Jeffrey N.
name: Herzog, Josef
name: Weeman, Kisa
name: Manoukian, Siranoush
name: Peissel, Bernard
name: Zaffaroni, Daniela
name: Scuvera, Giulietta
name: Bonanni, Bernardo
name: Mariette, Frederique
name: Volorio, Sara
name: Viel, Alessandra
name: Varesco, Liliana
name: Papi, Laura
name: Ottini, Laura
name: Tibiletti, Maria Grazia
name: Radice, Paolo
name: Yannoukakos, Drakoulis
name: Garber, Judy
name: Ellis, Steve
name: Frost, Debra
name: Platte, Radka
name: Fineberg, Elena
name: Evans, Gareth
name: Lalloo, Fiona
name: Izatt, Louise
name: Eeles, Ros
name: Adlard, Julian
name: Davidson, Rosemarie
name: Cole, Trevor
name: Eccles, Diana
name: Cook, Jackie
name: Hodgson, Shirley
name: Brewer, Carole
name: Tischkowitz, Marc
name: Douglas, Fiona
name: Porteous, Mary
name: Side, Lucy
name: Walker, Lisa
name: Morrison, Patrick
name: Donaldson, Alan
name: Kennedy, John
name: Foo, Claire
name: Godwin, Andrew K.
name: Schmutzler, Rita Katharina
name: Wappenschmidt, Barbara
name: Rhiem, Kerstin
name: Engel, Christoph
name: Meindl, Alfons
name: Ditsch, Nina
name: Arnold, Norbert
name: Plendl, Hans Jorg
name: Niederacher, Dieter
name: Sutter, Christian
name: Wang-Gohrke, Shan
name: Steinemann, Doris
name: Preisler-Adams, Sabine
name: Kast, Karin
name: Varon-Mateeva, Raymonda
name: Gehrig, Andrea
name: Stoppa-Lyonnet, Dominique
name: Sinilnikova, Olga M.
name: Mazoyer, Sylvie
name: Damiola, Francesca
name: Poppe, Bruce
name: Tucker, Kathy
name: Piedmonte, Marion
name: Claes, Kathleen
name: Backes, Floor
name: Rodriguez, Gustavo
name: Brewster, Wendy
name: Wakeley, Katie
name: Rutherford, Thomas
name: Caldes, Trinidad
name: Nevanlinna, Heli
name: Aittomaki, Kristiina
name: Rookus, Matti A.
name: Van Os, Theo A. M.
name: Kolk, Lizet Van Der
name: De Lange, J. L.
name: Meijers-Heijboer, Hanne E. J.
name: Van Der Hout, A. H.
name: Van Asperen, Christi J.
name: Gomez Garcia, Encarna B.
name: Hoogerbrugge, Nicoline
name: Collee, J. Margriet
name: Van Deurzen, Carolien H. M
name: Van Der Luijt, Rob B.
name: Devilee, Peter
name: Olah, Edith
name: Lazaro, Conxi
name: Teule, Alex
name: Menendez, Mireia
name: Jakubowska, Anna
name: Cybulski, Cezary
name: Gronwald, Jacek
name: Lubinski, Jan
name: Durda, Katarzyna
name: Jaworska-Bieniek, Katarzyna
name: Th. Johannson, Oskar
name: Maugard, Christine
name: Montagna, Marco
name: Tognazzo, Silvia
name: Teixeira, Manuel R.
name: Healey, Sue
name: Olswald, Curtis
name: Guidugli, Lucia
name: Slager, Susan
name: Lindor, Noralane
name: Szabo, Csilla I.
name: Vijai, Joseph
name: Kauff, Noah
name: Fink-Retter, Anneliese
name: Zhang, Liying
name: Rau-Murthy, Rohini
name: Robson, Mark
name: Rappaport, Christine
name: Singer, Christian F.
name: Tea, Muy-Kheng
name: Kaulich, Daphne Geschwantler
name: Berger, Andreas
name: Pfeiler, Georg
name: Mai, Phuong L.
name: Phelan, Catherine M.
name: Lejbkowicz, Flavio
name: Greene, Mark H.
name: Andrulis, Irene
name: Mulligan, Anna Marie
name: Glendon, Gord
name: Toland, Amanda Ewart
name: Bojeson, Anders
name: Pederson, Inge Sokilde
name: Sunde, Lone
name: Thomassen, Mads
name: Kruse, Torben A.
name: Jensen, Uffe Birk
name: Friedman, Eitan
name: Laitman, Yael
name: Shimon, Shani Paluch
name: Simard, Jacques
name: Offit, Kenneth
name: Easton, Douglas F.
name: Chenevix-Trench, Georgia
name: Antoniou, Antonis C.
name: Benitez, Javier
name: Couch, Fergus J.
Publisher: name: Columbia University
Year: 2014
Subjects: subject: Cancer--Risk factors
subject: Cancer--Genetic aspects
subject: Genetics
subject: FOS: Biological sciences
subject: Single nucleotide polymorphisms
subject: Biology

description: 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&lt;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.