DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers Journal Article
| Authors: | Osorio, A.; Milne, R. L.; Kuchenbaecker, K.; Vaclová, 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, S. M.; Lester, J.; John, E. M.; Whittemore, A. S.; Daly, M. B.; 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. O.; 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.; Grazia Tibiletti, M.; 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, C.; 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.; Meindel, 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. M.; van der Kolk, L.; de Lange, J. L.; Meijer-Heijboer, H. E. J.; van der Hout, A. H.; van Asperen, C. J.; Gomez Garcia, E. B.; Hoogerbrugge, N.; Collee, J. M.; van Deurzen, C. H. M.; 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.; kConFab Investigators; 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.; Ewart Toland, A.; Bojesen, A.; Pedersen, 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. |
| Article Title: | DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers |
| 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. © 2014. |
| Keywords: | adult; gene mutation; major clinical study; single nucleotide polymorphism; cancer risk; genetic analysis; disease association; ovary cancer; breast cancer; genetic association; genetic variability; genotype; gene function; brca1 protein; brca2 protein; heterozygote; oncogene; gene identification; excision repair; dna glycosyltransferase; lig3 gene; human; female; article; 8 guanine dna glycosylase gene; apex1 gene; apex2 gene; endonuclease viii like 2 gene; mbd4 gene; mpg gene; mutyh gene; neil1 gene; neil2 gene; nthl1 gene; ogg1 gene; parp1 gene; parp2 gene; pnkp gene; polb gene; sequence tagged site; smug1 gene; tdg gene; ung gene; xrcc1 gene |
| Journal Title: | PLoS Genetics |
| Volume: | 10 |
| Issue: | 4 |
| ISSN: | 1553-7390 |
| Publisher: | Public Library of Science |
| Date Published: | 2014-04-01 |
| Start Page: | e1004256 |
| Language: | English |
| DOI: | 10.1371/journal.pgen.1004256 |
| PROVIDER: | scopus |
| PMCID: | PMC3974638 |
| PUBMED: | 24698998 |
| DOI/URL: | |
| Notes: | PLoS Genet. -- Export Date: 8 July 2014 -- Source: Scopus |
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