A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers

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 canc...

Descripción completa

Detalles Bibliográficos
Autores: Baquero, Juan Miguel, Benitez-Buelga, Carlos, Fernández, Victoria, Urioste, Miguel, García-Giménez, José Luis, Perona Abellón, Rosario, CIMBA Consortium, Benítez, Javier, Osorio, Ana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/188680
Acceso en línea:http://hdl.handle.net/10261/188680
Access Level:acceso abierto
Palabra clave:BRCA2
DNA damage
Cancer risk modifier
Oxidative stress susceptibility
Telomere damage
Uracil-DNA glycosylase
Descripción
Sumario: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.

Similares en LA Referencia