2026-06-14T03:33:49Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/78402025-05-13T11:16:47Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Baquero, Juan Miguel
author
Benítez-Buelga, Carlos
author
Fernández, Victoria
author
Urioste, Miguel
author
García-Giménez, Jose Luis
author
Perona, Rosario
author
Benitez, Javier
author
Osorio, Ana
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Instituto de Salud Carlos III
2019-07-03T06:26:07Z
2019-07-03T06:26:07Z
2019-05
Mol Oncol. 2019;13(5):1110-1120.
10.1002/1878-0261.12470
1878-0261
15747891
Molecular oncology
30747491
http://hdl.handle.net/20.500.12105/7840
Single nucleotide polymorphisms (SNPs) in DNA glycosylase genes involved in the base excision repair (BER) pathway can modify breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We previously found that SNP rs34259 in the uracil-DNA glycosylase gene (UNG) might decrease ovarian cancer risk in BRCA2 mutation carriers. In the present study, we validated this finding in a larger series of familial breast and ovarian cancer patients to gain insights into how this UNG variant exerts its protective effect. We found that rs34259 is associated with significant UNG downregulation and with lower levels of DNA damage at telomeres. In addition, we found that this SNP is associated with significantly lower oxidative stress susceptibility and lower uracil accumulation at telomeres in BRCA2 mutation carriers. Our findings help to explain the association of this variant with a lower cancer risk in BRCA2 mutation carriers and highlight the importance of genetic changes in BER pathway genes as modifiers of cancer susceptibility for BRCA1 and BRCA2 mutation carriers.
eng
BRCA2
DNA damage
Cancer risk modifier
Oxidative stress susceptibility
Telomere damage
Uracil-DNA glycosylase
A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers
journal article
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