DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers
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Date
Authors
Osorio, Ana
Milne, Roger L.
Kuchenbaecker, Karoline B.
Vaclova, Tereza
Pita, Guillermo
Alonso, Rosario
Peterlongo, Paolo
Blanco, Ignacio
De la Hoya, Miguel
Duran, Mercedes
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
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 = 2.761023) 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 = 4.861023). 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.
Description
Keywords
Genes, Cancer risk in carriers, Single nucleotide polymorphism (SNP), Base excision repair (BER)
Sustainable Development Goals
Citation
Osorio A, Milne RL, Kuchenbaecker K, Vaclova, T, Pita G, et al. (2014) DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. PLoS Genet 10(4): e1004256. doi:10.1371/journal.pgen.1004256.