Open AccessA common SNP in the UNG gene decreases ovarian cancer risk in BRCA 2 mutation carriers
Author(s) -
Baquero Juan Miguel,
BenítezBuelga Carlos,
Fernández Victoria,
Urioste Miguel,
GarcíaGiménez Jose Luis,
Perona Rosario,
Benítez Javier,
Osorio Ana
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12470
Subject(s) - ovarian cancer , single nucleotide polymorphism , brca mutation , snp , mutation , breast cancer , cancer research , cancer , biology , genetics , base excision repair , dna repair , gene , genotype
Single nucleotide polymorphisms ( SNP s) in DNA glycosylase genes involved in the base excision repair ( BER ) pathway can modify breast and ovarian cancer risk in BRCA 1 and BRCA 2 mutation carriers. We previously found that SNP rs34259 in the uracil‐ DNA glycosylase gene ( UNG ) might decrease ovarian cancer risk in BRCA 2 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 BRCA 2 mutation carriers. Our findings help to explain the association of this variant with a lower cancer risk in BRCA 2 mutation carriers and highlight the importance of genetic changes in BER pathway genes as modifiers of cancer susceptibility for BRCA 1 and BRCA 2 mutation carriers.