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oai:repisalud.isciii.es:20.500.12105/78402025-05-13T11:16:47Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2019-05 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. 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 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