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...
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doaj-a5aa8022a3784ff59df336ceef7e075d2020-11-25T02:36:41ZengWileyMolecular Oncology1574-78911878-02612019-05-011351110112010.1002/1878-0261.12470A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriersJuan Miguel Baquero0Carlos Benítez‐Buelga1Victoria Fernández2Miguel Urioste3Jose Luis García‐Giménez4Rosario Perona5the CIMBA Consortium6Javier Benítez7Ana Osorio8Human Genetics Group Spanish National Cancer Research Centre (CNIO) Madrid SpainHelleday Laboratory Department of Oncology‐Pathology Karolinska Institutet Solna SwedenHuman Genetics Group Spanish National Cancer Research Centre (CNIO) Madrid SpainSpanish Network on Rare Diseases (CIBERER) Madrid SpainSpanish Network on Rare Diseases (CIBERER) Madrid SpainSpanish Network on Rare Diseases (CIBERER) Madrid SpainConsortium of Investigators of Modifiers of BRCA1/2Human Genetics Group Spanish National Cancer Research Centre (CNIO) Madrid SpainHuman Genetics Group Spanish National Cancer Research Centre (CNIO) Madrid SpainSingle 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.https://doi.org/10.1002/1878-0261.12470BRCA2cancer risk modifierDNA damageoxidative stress susceptibilitytelomere damageuracil‐DNA glycosylase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juan Miguel Baquero Carlos Benítez‐Buelga Victoria Fernández Miguel Urioste Jose Luis García‐Giménez Rosario Perona the CIMBA Consortium Javier Benítez Ana Osorio |
spellingShingle |
Juan Miguel Baquero Carlos Benítez‐Buelga Victoria Fernández Miguel Urioste Jose Luis García‐Giménez Rosario Perona the CIMBA Consortium Javier Benítez Ana Osorio A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers Molecular Oncology BRCA2 cancer risk modifier DNA damage oxidative stress susceptibility telomere damage uracil‐DNA glycosylase |
author_facet |
Juan Miguel Baquero Carlos Benítez‐Buelga Victoria Fernández Miguel Urioste Jose Luis García‐Giménez Rosario Perona the CIMBA Consortium Javier Benítez Ana Osorio |
author_sort |
Juan Miguel Baquero |
title |
A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers |
title_short |
A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers |
title_full |
A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers |
title_fullStr |
A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers |
title_full_unstemmed |
A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers |
title_sort |
common snp in the ung gene decreases ovarian cancer risk in brca2 mutation carriers |
publisher |
Wiley |
series |
Molecular Oncology |
issn |
1574-7891 1878-0261 |
publishDate |
2019-05-01 |
description |
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. |
topic |
BRCA2 cancer risk modifier DNA damage oxidative stress susceptibility telomere damage uracil‐DNA glycosylase |
url |
https://doi.org/10.1002/1878-0261.12470 |
work_keys_str_mv |
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