Journal
PLOS GENETICS
Volume 10, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1004256
Keywords
-
Categories
Funding
- Mutua Madrilena Foundation (FMMA)
- Spanish Association against Cancer [AECC08]
- RTICC [06/0020/1060]
- European Community [223175 (HEALTH-F2-2009-223175)]
- Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692, C1287/A11990, C5047/A8385]
- National Institutes of Health [CA128978]
- Post-Cancer GWAS initiative [1 U19 CA 148537]
- Department of Defence [W81XWH-10-1-0341]
- Canadian Institutes of Health Research (CIHR)
- Komen Foundation for the Cure
- Breast Cancer Research Foundation
- Ovarian Cancer Research Fund
- Swedish Cancer Society
- Cancer Association of South Africa (CANSA)
- NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA125183, R01 CA142996, 1U01CA161032, CA116201]
- Ralph and Marion Falk Medical Research Trust
- Entertainment Industry Fund National Women's Cancer Research Alliance
- Basser Research Center
- American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]
- National Cancer Institute [UM1 CA164920, CA 27469, CA 101165, CA 37517]
- Lithuania (BFBOCC-LT): Research Council of Lithuania [LIG-07/2012]
- Hereditary Cancer Association (Paveldimo vezio asociacija)
- LSC [10.0010.08]
- ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]
- Liepaja's municipal council
- Morris and Horowitz Families Professorship
- NEYE Foundation
- City of Hope Clinical Cancer Genetics Community Research Network, National Cancer Institute [RC4A153828]
- Office of the Director, National Institutes of Health
- Italian Association for Cancer Research (AIRC)
- FiorGen Foundation for Pharmacogenomics
- Associazione CAOS Varese
- European Union (European Social Fund - ESF)
- Greek national funds through the Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA
- NIHR
- University of Kansas Cancer Center [P30 CA168524]
- Kansas Bioscience Authority Eminent Scholar Program
- Chancellors Distinguished Chair in Biomedical Sciences Professorship
- German Cancer Aid [109076]
- Center for Molecular Medicine Cologne (CMMC)
- Ligue National Contre le Cancer
- Association Le cancer du sein, parlons-en! Award
- Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program
- Intramural Research Program, NCI
- RTICC (ISCIII), Spanish Ministry of Economy and Competitivity [RD06/0020/0021]
- Helsinki University Central Hospital Research Fund
- Academy of Finland [132473]
- Finnish Cancer Society
- Sigrid Juselius Foundation
- Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]
- Netherlands Organization of Scientific Research [NWO 91109024]
- Pink Ribbon grant [110005]
- BBMRI [NWO 184.021.007/CP46]
- Hungarian Research Grant KTIA-OTKA [CK-80745]
- Polish Foundation of Science
- Nordic Cancer Union, Icelandic Association Walking for Breast Cancer Research
- Landspitali University Hospital Research Fund
- Canadian Institutes of Health Research
- Canadian Breast Cancer Research Alliance-grant [019511]
- Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]
- Ministero dell'Istruzione, dell'Universitae della Ricerca and Ministero della Salute
- National Breast Cancer Foundation
- National Health and Medical Research Council (NHMRC)
- Queensland Cancer Fund
- Cancer Councils of New South Wales, Victoria
- NIH [CA128978]
- U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]
- Sharon Levine Corzine Fund
- Niehaus Clinical Cancer Genetics Initiative
- Andrew Sabin Family Foundation
- Lymphoma Foundation
- US National Cancer Institute, NIH
- Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]
- Clalit Health Services in Israel
- Israel Cancer Association
- Breast Cancer Research Foundation (BCRF), NY
- Ohio State University Comprehensive Cancer Center
- [FISPI12/00070]
- [5U01CA113916]
- [R01CA140323]
- Cancer Research UK [17528, 11174, 11022, 16563, 10118, 17523, 15007] Funding Source: researchfish
- National Breast Cancer Foundation [IF-12-06] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10096] Funding Source: researchfish
Ask authors/readers for more resources
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 = 2.7x10(-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 = 4.8x10(-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.
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