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Molecular insights into the OGG1 gene, a cancer risk modifier in BRCA1 and BRCA2 mutations carriers

Published on May 3, 2016in Oncotarget
· DOI :10.18632/oncotarget.8272
Carlos Benitez-Buelga4
Estimated H-index: 4
,
Tereza Vaclova3
Estimated H-index: 3
+ 6 AuthorsJavier Benitez72
Estimated H-index: 72
Cite
Abstract
// Carlos Benitez-Buelga 1 , Tereza Vaclova 1 , Sofia Ferreira 1 , Miguel Urioste 2, 5 , Lucia Inglada-Perez 3, 5 , Nora Soberon 4 , Maria A. Blasco 4 , Ana Osorio 1, 5 , Javier Benitez 1, 5 1 Human Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain 2 Familial Cancer Clinical Unit, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain 3 Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain 4 Telomere and Telomerase Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain 5 Spanish Network on Rare Diseases (CIBERER), Madrid 28029, Spain Correspondence to: Javier Benitez, e-mail: jbenitez@cnio.es Keywords: BRCA1 and BRCA2, telomere shortening, OGG1 polymorfism, cancer risk modifier, DNA damage Received: January 28, 2016      Accepted: March 07, 2016      Published: March 22, 2016 ABSTRACT We have recently shown that rs2304277 variant in the OGG1 glycosidase gene of the Base Excision Repair pathway can increase ovarian cancer risk in BRCA1 mutation carriers. In the present study, we aimed to explore the role of this genetic variant on different genome instability hallmarks to explain its association with cancer risk. We have evaluated the effect of this polymorphism on OGG1 transcriptional regulation and its contribution to telomere shortening and DNA damage accumulation. For that, we have used a series of 89 BRCA1 and BRCA2 mutation carriers, 74 BRCAX cases, 60 non-carrier controls and 23 lymphoblastoid cell lines (LCL) derived from BRCA1 mutation carriers and non-carriers. We have identified that this SNP is associated to a significant OGG1 transcriptional down regulation independently of the BRCA mutational status and that the variant may exert a synergistic effect together with BRCA1 or BRCA2 mutations on DNA damage and telomere shortening. These results suggest that this variant, could be associated to a higher cancer risk in BRCA1 mutation carriers, due to an OGG1 transcriptional down regulation and its effect on genome instability.
  • References (35)
  • Citations (7)
Cite
References35
Newest
Published on Jan 1, 2016in Cancer Research 8.38
Larysa V. Yuzefovych7
Estimated H-index: 7
(USA: University of South Alabama),
Andrea G. Kahn5
Estimated H-index: 5
(USA: University of South Alabama)
+ 5 AuthorsLyudmila I. Rachek13
Estimated H-index: 13
(USA: University of South Alabama)
Production of mitochondrial reactive oxygen species and integrity of mitochondrial DNA (mtDNA) are crucial in breast cancer progression and metastasis. Therefore, we evaluated the role of mtDNA damage in breast cancer by genetically modulating the DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1) in the PyMT transgenic mouse model of mammary tumorigenesis. We generated mice lacking OGG1 (KO), mice overexpressing human OGG1 subunit 1alpha in mitochondria (Tg), and mice simultaneously lacking ...
Published on Jul 1, 2015in Breast Cancer Research and Treatment 3.47
Tereza Vaclova3
Estimated H-index: 3
,
Gonzalo Gómez-López8
Estimated H-index: 8
+ 7 AuthorsAna Osorio42
Estimated H-index: 42
BRCA1 germline mutations increase the lifetime risk of developing breast and ovarian cancers. However, taking into account the differences in disease manifestation among mutation carriers, it is probable that different BRCA1 mutations have distinct haploinsufficiency effects and lead to the formation of different phenotypes. Using lymphoblastoid cell lines derived from heterozygous BRCA1 mutation carriers and non-carriers, we investigated the haploinsufficiency effects of various mutation types ...
Published on Apr 30, 2015in Nucleic Acids Research 11.15
Jia Zhou7
Estimated H-index: 7
(UVM: University of Vermont),
Aaron M. Fleming21
Estimated H-index: 21
(UofU: University of Utah)
+ 2 AuthorsSusan S. Wallace47
Estimated H-index: 47
(UVM: University of Vermont)
G-quadruplex is a four-stranded G-rich DNA structure that is highly susceptible to oxidation. Despite the important roles that G-quadruplexes play in telomere biology and gene transcription, neither the impact of guanine lesions on the stability of quadruplexes nor their repair are well understood. Here, we show that the oxidized guanine lesions 8-oxo-7,8-dihydroguanine (8-oxoG), guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) reduce the thermostability and alter the folding of telomeric ...
Published on Jan 1, 2015in Journal of Molecular and Cellular Cardiology 5.05
Marte Bliksøen7
Estimated H-index: 7
(University of Oslo),
Anton Baysa7
Estimated H-index: 7
(University of Oslo)
+ 5 AuthorsGuro Valen30
Estimated H-index: 30
(University of Oslo)
Abstract Ischemia–reperfusion (IR) injury of the heart generates reactive oxygen species that oxidize macromolecules including mitochondrial DNA (mtDNA). The 8-oxoguanine DNA glycosylase (OGG1) works synergistically with MutY DNA glycosylase (MYH) to maintain mtDNA integrity. Our objective was to study the functional outcome of lacking the repair enzymes OGG1 and MYH after myocardial IR and we hypothesized that OGG1 and MYH are important enzymes to preserve mtDNA and heart function after IR. Ex ...
Published on Jan 1, 2015in Breast Cancer Research and Treatment 3.47
Carlos Benitez-Buelga4
Estimated H-index: 4
,
Lara Sánchez-Barroso4
Estimated H-index: 4
+ 12 AuthorsRosario Perona28
Estimated H-index: 28
(CSIC: Spanish National Research Council)
Recently, we observed that telomeres of BRCA1/2 mutation carriers were shorter than those of controls or sporadic breast cancer patients, suggesting that mutations in these genes might be responsible for this event. Given the contradictory results reported in the literature, we tested whether other parameters, such as chemotherapy, could be modifying telomere length (TL). We performed a cross-sectional study measuring leukocyte TL of 266 sporadic breasts cancer patients treated with first-line c...
Published on Dec 1, 2014in Carcinogenesis 4.00
Boris M. Brenerman2
Estimated H-index: 2
(NIH: National Institutes of Health),
Jennifer L. Illuzzi6
Estimated H-index: 6
(NIH: National Institutes of Health),
David M. Wilson48
Estimated H-index: 48
(NIH: National Institutes of Health)
Base excision repair (BER) is a frontline defense mechanism for dealing with many common forms of endogenous DNA damage, several of which can drive mutagenic or cell death outcomes. The pathway engages proteins such as glycosylases, abasic endonucleases, polymerases and ligases to remove substrate modifications from DNA and restore the genome back to its original state. Inherited mutations in genes related to BER can give rise to disorders involving cancer, immunodeficiency and neurodegeneration...
Published on Oct 29, 2014in PLOS ONE 2.78
Elisa Coluzzi4
Estimated H-index: 4
,
Monica Colamartino3
Estimated H-index: 3
+ 4 AuthorsAntonella Sgura17
Estimated H-index: 17
One main function of telomeres is to maintain chromosome and genome stability. The rate of telomere shortening can be accelerated significantly by chemical and physical environmental agents. Reactive oxygen species are a source of oxidative stress and can produce modified bases (mainly 8-oxoG) and single strand breaks anywhere in the genome. The high incidence of guanine residues in telomeric DNA sequences makes the telomere a preferred target for oxidative damage. Our aim in this work is to eva...
Published on Jun 1, 2014in Carcinogenesis 4.00
Eva Moritz4
Estimated H-index: 4
(University of Mainz),
Karin Pauly5
Estimated H-index: 5
+ 3 AuthorsBernd Epe43
Estimated H-index: 43
The repair of 8-oxo-7,8-dihydroguanine in the DNA of mammalian cells is initiated by 8-oxoguanine DNA glycosylase (OGG1). A frequent polymorphism in the human OGG1 gene, rs1052133, causes the substitution of serine by cysteine at amino acid 326 of the protein and has been associated with an altered risk for various types of cancer in some populations. The OGG1-Cys326 protein appears to have normal enzymatic activity, but greater sensitivity to oxidation than the serine variant. Here, we describe...
Published on Apr 3, 2014in PLOS Genetics 5.22
Ana Osorio42
Estimated H-index: 42
,
Roger L. Milne56
Estimated H-index: 56
(Cancer Council Victoria)
+ 194 AuthorsMercedes Durán21
Estimated H-index: 21
(University of Valladolid)
Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging...
Published on Dec 15, 2013in Human Molecular Genetics 4.54
Karen A. Pooley34
Estimated H-index: 34
(University of Cambridge),
Stig E. Bojesen60
Estimated H-index: 60
(UCPH: University of Copenhagen)
+ 32 AuthorsJudith Brown24
Estimated H-index: 24
(University of Cambridge)
Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the "iCOGS" custom genotyping array. All ~200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL association (...
Cited By7
Newest
Published on Sep 1, 2019in Cancer Genetics and Cytogenetics 2.18
Shahzad Yousaf1
Estimated H-index: 1
,
Asad Ullah Khan10
Estimated H-index: 10
+ 4 AuthorsIshrat Mahjabeen9
Estimated H-index: 9
Published on Jun 1, 2019in DNA Repair 3.71
Mohammad Mirza-Aghazadeh-Attari3
Estimated H-index: 3
(Tabriz University of Medical Sciences),
Caspian Ostadian (Urmia University)+ 7 AuthorsMaryam Majidinia (Urmia University of Medical Sciences)
Abstract Ovarian cancer is among the most lethal gynecologic malignancies with a poor survival prognosis. The current therapeutic strategies involve surgery and chemotherapy. Research is now focused on novel agents especially those targeting DNA damage response (DDR) pathways. Understanding the DDR process in ovarian cancer necessitates having a detailed knowledge on a series of signaling mediators at the cellular and molecular levels. The complexity of the DDR process in ovarian cancer and how ...
Published on May 1, 2019in Molecular Oncology 5.96
Juan Miguel Baquero1
Estimated H-index: 1
,
Carlos Benitez-Buelga4
Estimated H-index: 4
(KI: Karolinska Institutet)
+ 5 AuthorsAna Osorio42
Estimated H-index: 42
Published on Sep 1, 2018in The Journal of Pathology 5.94
Vassilis G. Gorgoulis45
Estimated H-index: 45
(UoA: National and Kapodistrian University of Athens),
Dafni-Eleftheria Pefani7
Estimated H-index: 7
(University of Oxford)
+ 1 AuthorsΙωάννης Π. Τρουγκάκος30
Estimated H-index: 30
(UoA: National and Kapodistrian University of Athens)
Published on Mar 1, 2018in Annals of Human Genetics 1.32
T. Ahmed (CUI: COMSATS Institute of Information Technology), S. Nawaz (BZU: Bahauddin Zakariya University)+ 11 AuthorsA.A. Qureshi1
Estimated H-index: 1
(Boston Children's Hospital)
Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 200 UBC cases and 200 controls. W...
Published on Jan 1, 2018in Journal of the Academy of Nutrition and Dietetics 4.14
Dolores Corella69
Estimated H-index: 69
,
Judith B. Ramírez‐Sabio2
Estimated H-index: 2
+ 19 AuthorsLuis Fernando Aros Borau46
Estimated H-index: 46
Abstract Background Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 ( OGG1 ). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1 -rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet. Objective Our aim was to evaluate the association of the OGG1 -rs1052133 with total, cancer, and ...
Published on Jun 1, 2017in Free Radical Biology and Medicine 5.66
Mariarosaria D’Errico8
Estimated H-index: 8
(ISS: Istituto Superiore di Sanità),
Eleonora Parlanti14
Estimated H-index: 14
(ISS: Istituto Superiore di Sanità)
+ 4 AuthorsEugenia Dogliotti40
Estimated H-index: 40
(ISS: Istituto Superiore di Sanità)
Abstract Oxidative stress is associated with a growing number of diseases that span from cancer to neurodegeneration. Most oxidatively induced DNA base lesions are repaired by the base excision repair (BER) pathway which involves the action of various DNA glycosylases. There are numerous genome wide studies attempting to associate single-nucleotide polymorphisms (SNPs) with predispositions to various types of disease; often, these common variants do not have significant alterations in their bioc...
Published on Jun 1, 2017in Free Radical Biology and Medicine 5.66
Serge Boiteux46
Estimated H-index: 46
(CNRS: Centre national de la recherche scientifique),
Franck Coste10
Estimated H-index: 10
(CNRS: Centre national de la recherche scientifique),
Bertrand Castaing14
Estimated H-index: 14
(CNRS: Centre national de la recherche scientifique)
Abstract Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2–6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutage...
Published on Apr 1, 2017in Cancer Research 8.38
Avrum Spira36
Estimated H-index: 36
(BU: Boston University),
Matthew B. Yurgelun14
Estimated H-index: 14
(Harvard University)
+ 17 AuthorsMadhav V. Dhodapkar56
Estimated H-index: 56
(Yale Cancer Center)
Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. In this Perspective, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity – basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations ha...