Centers and Institutes
Published April 3, 2014 | Version v1
Journal article Open

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

Creators

  • 1. Biomedical Network on Rare Diseases
  • 2. Cancer Council Victoria
  • 3. University of Cambridge
  • 4. Spanish National Cancer Centre
  • 5. Fondazione Istituto FIRC di Oncologia Molecolare
  • 6. IDIBELL-Catalan Institute of Oncology
  • 7. Hospital Clinico San Carlos
  • 8. Universidad de Valladolid
  • 9. Universitat Autonoma de Barcelona
  • 10. Hospital de la Santa Creu i Sant Pau
  • 11. National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis
  • 12. Cruces Hospital Barakaldo
  • 13. Hospital Clínico Lozano Blesa
  • 14. Centre Hospitalier Universitaire de Québec and Laval University
  • 15. University of Chicago

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<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.

Notes

Due to the large number of authors, only the first 20 and the University of Chicago authors are included on the above author list. Please download the article for the complete list of authors.

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Additional details

Identifiers

DOI
10.1371/journal.pgen.1004256
Other
oai:uchicago.tind.io:10884

Funding

Mutua Madrileña Foundation
Spanish Association against Cancer
RTICC
06/0020/1060
RTICC
FISPI12/00070
European Community
Seventh Framework Programme
Cancer Research UK
C1287/A10118
Cancer Research UK
C1287/A 10710
Cancer Research UK
C12292/A11174
Cancer Research UK
C5047/A8384
Cancer Research UK
C5047/A15007
Cancer Research UK
C5047/A10692
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
Komen Foundation for the Cure
Breast Cancer Research Foundation
Ovarian Cancer Research Fund
Swedish Cancer Society
Cancer Association of South Africa
National Cancer Institute
Specialized Program of Research Excellence in Breast Cancer
National Cancer Institute
R01 CA142996
National Cancer Institute
1U01CA161032
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
National Cancer Institute
UM1 CA164920
Research Council of Lithuania
LIG-07/2012
Hereditary Cancer Association
LSC
10.0010.08
ESF
Nr.2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016
National Institutes of Health
R01CA74415
National Institutes of Health
P30 CA033752
Morris and Horowitz Families
Professorship
NEYE Foundation
National Cancer Institute
RC4A153828
Italian Association for Cancer Research
FiorGen Foundation for Pharmacogenomics
Associazione CAOS Varese
Italian citizens
European Union
European Social Fund
Greek national funds
Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework
Hellenic Cooperative Oncology Group
Hellenic Foundation for Cancer Research
Cancer Research UK
C1287/A11990
National Institute for Health and Care Research
Cancer Research UK
C5047/A8385
University of Kansas
Cancer Center
Kansas Bioscience Authority
Eminent Scholar Program
Unknown funder
5U01CA113916
Unknown funder
R01CA140323
Unknown funder
Chancellors Distinguished Chair in Biomedical Sciences Professorship
German Cancer Aid
109076
Center for Molecular Medicine Cologne
Ligue National Contre le Cancer
Association "Le cancer du sein, parlons-en!"
Canadian Institutes of Health Research
"CIHR Team in Familial Risks of Breast Cancer” program
National Cancer Institute
CA 27469
GOG
Statistical and Data Center
GOG
Cancer Prevention and Control Committee
National Cancer Institute
Intramural Research Program
National Cancer Institute
CA 37517
National Cancer Institute
CA 101165
RTICC
RD06/0020/0021
Helsinki University
Hospital Research Fund
Academy of Finland
132473
Finnish Cancer Society
Sigrid Juselius Foundation
Dutch Cancer Society
NKI1998-1854
Dutch Cancer Society
NKI2004-3088
Dutch Cancer Society
NKI2007-3756
Netherlands Organization of Scientific Research
NWO 91109024
Pink Ribbon
110005
BBMRI
NWO 184.021.007/CP46
Unknown funder
Hungarian Research Grant
Polish Foundation of Science
Nordic Cancer Union
Icelandic Association
"Walking for Breast Cancer Research"
Landspitali University Hospital
Research Fund
Canadian Institutes of Health
"CIHR Team in Familial Risks of Breast Cancer" program
Canadian Breast Cancer Research Alliance
019511
Ministry of Economic Development, Innovation and Export Trade
PSR-SIIRI-701
Ministero dell'Istruzione
National Breast Cancer Foundation
National Health and Medical Research Council
Queensland
Cancer Fund
Cancer Councils of New South Wales, Victoria, Tasmania and South Australia
Cancer Foundation of Western Australia
National Cancer Institute
Specialized Program of Research Excellence in Breast Cancer
U.S. Department of Defence
Ovarian Cancer Idea award
Sharon Levine Corzine
Niehaus Clinical Cancer Genetics Initiative
Andrew Sabin Family Foundation
Lymphoma Foundation
Westat, Inc.
NO2-CP-11019-50
Westat, Inc.
N02-CP-65504
Clalit Health Services
Israel Cancer Association
Ohio State University

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine
Center(s) or Institute(s)
Center for Clinical Cancer Genetics and Global Health