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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

Osorio, Ana; Milne, Roger L; Kuchenbaecker, Karoline; Vaclová, Tereza; Pita, Guillermo; Alonso, Rosario; Peterlongo, Paolo; Blanco, Ignacio; de la Hoya, Miguel and Duran, Mercedes, et al. (2014) In PLoS Genetics 10(4).
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... (More)
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. (Less)
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4
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Public Library of Science
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  • pmid:24698998
  • wos:000335499600026
  • scopus:84901332067
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1553-7404
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10.1371/journal.pgen.1004256
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English
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@article{cdf6fb07-70be-42fb-89ad-4506e832110d,
  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&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.},
  articleno    = {e1004256},
  author       = {Osorio, Ana and Milne, Roger L and Kuchenbaecker, Karoline and Vaclová, Tereza and Pita, Guillermo and Alonso, Rosario and Peterlongo, Paolo and Blanco, Ignacio and de la Hoya, Miguel and Duran, Mercedes and Díez, Orland and Ramón Y Cajal, Teresa and Konstantopoulou, Irene and Martínez-Bouzas, Cristina and Andrés Conejero, Raquel and Soucy, Penny and McGuffog, Lesley and Barrowdale, Daniel and Lee, Andrew and Swe-Brca, Swe-Brca and Arver, Brita and Rantala, Johanna and Loman, Niklas and Ehrencrona, Hans and Olopade, Olufunmilayo I and Beattie, Mary S and Domchek, Susan M and Nathanson, Katherine and Rebbeck, Timothy R and Arun, Banu K and Karlan, Beth Y and Walsh, Christine and Lester, Jenny and John, Esther M and Whittemore, Alice S and Daly, Mary B and Southey, Melissa and Hopper, John and Terry, Mary B and Buys, Saundra S and Janavicius, Ramunas and Dorfling, Cecilia M and van Rensburg, Elizabeth J and Steele, Linda and Neuhausen, Susan L and Ding, Yuan Chun and Hansen, Thomas V O and Jønson, Lars and Ejlertsen, Bent and Gerdes, Anne-Marie and Infante, Mar and Herráez, Belén and Moreno, Leticia Thais and Weitzel, Jeffrey N and Herzog, Josef and Weeman, Kisa and Manoukian, Siranoush and Peissel, Bernard and Zaffaroni, Daniela and Scuvera, Giulietta and Bonanni, Bernardo and Mariette, Frederique and Volorio, Sara and Viel, Alessandra and Varesco, Liliana and Papi, Laura and Ottini, Laura and Tibiletti, Maria Grazia and Radice, Paolo and Yannoukakos, Drakoulis and Garber, Judy and Ellis, Steve and Frost, Debra and Platte, Radka and Fineberg, Elena and Evans, Gareth and Lalloo, Fiona and Izatt, Louise and Eeles, Ros and Adlard, Julian and Davidson, Rosemarie and Cole, Trevor and Eccles, Diana and Cook, Jackie and Hodgson, Shirley and Brewer, Carole and Tischkowitz, Marc and Douglas, Fiona and Porteous, Mary and Side, Lucy and Walker, Lisa and Morrison, Patrick and Donaldson, Alan and Kennedy, John and Foo, Claire and Godwin, Andrew K and Schmutzler, Rita Katharina and Wappenschmidt, Barbara and Rhiem, Kerstin and Engel, Christoph and Meindl, Alfons and Ditsch, Nina and Arnold, Norbert and Plendl, Hans Jörg and Niederacher, Dieter and Sutter, Christian and Wang-Gohrke, Shan and Steinemann, Doris and Preisler-Adams, Sabine and Kast, Karin and Varon-Mateeva, Raymonda and Gehrig, Andrea and Stoppa-Lyonnet, Dominique and Sinilnikova, Olga M and Mazoyer, Sylvie and Damiola, Francesca and Poppe, Bruce and Claes, Kathleen and Piedmonte, Marion and Tucker, Kathy and Backes, Floor and Rodríguez, Gustavo and Brewster, Wendy and Wakeley, Katie and Rutherford, Thomas and Caldés, Trinidad and Nevanlinna, Heli and Aittomäki, Kristiina and Rookus, Matti A and van Os, Theo A M and van der Kolk, Lizet and de Lange, J L and Meijers-Heijboer, Hanne E J and van der Hout, A H and van Asperen, Christi J and Gómez Garcia, Encarna B and Hoogerbrugge, Nicoline and Collée, J Margriet and van Deurzen, Carolien H M and van der Luijt, Rob B and Devilee, Peter and Hebon, Hebon and Olah, Edith and Lázaro, Conxi and Teulé, Alex and Menéndez, Mireia and Jakubowska, Anna and Cybulski, Cezary and Gronwald, Jacek and Lubinski, Jan and Durda, Katarzyna and Jaworska-Bieniek, Katarzyna and Johannsson, Oskar Th and Maugard, Christine and Montagna, Marco and Tognazzo, Silvia and Teixeira, Manuel R and Healey, Sue and Investigators, Kconfab and Olswold, Curtis and Guidugli, Lucia and Lindor, Noralane and Slager, Susan and Szabo, Csilla I and Vijai, Joseph and Robson, Mark and Kauff, Noah and Zhang, Liying and Rau-Murthy, Rohini and Fink-Retter, Anneliese and Singer, Christian F and Rappaport, Christine and Geschwantler Kaulich, Daphne and Pfeiler, Georg and Tea, Muy-Kheng and Berger, Andreas and Phelan, Catherine M and Greene, Mark H and Mai, Phuong L and Lejbkowicz, Flavio and Andrulis, Irene and Mulligan, Anna Marie and Glendon, Gord and Toland, Amanda Ewart and Bojesen, Anders and Pedersen, Inge Sokilde and Sunde, Lone and Thomassen, Mads and Kruse, Torben A and Jensen, Uffe Birk and Friedman, Eitan and Laitman, Yael and Shimon, Shani Paluch and Simard, Jacques and Easton, Douglas F and Offit, Kenneth and Couch, Fergus J and Chenevix-Trench, Georgia and Antoniou, Antonis C and Benitez, Javier},
  issn         = {1553-7404},
  language     = {eng},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS Genetics},
  title        = {DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.},
  url          = {http://dx.doi.org/10.1371/journal.pgen.1004256},
  volume       = {10},
  year         = {2014},
}