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

authors

  • Benitez Buelga, Carlos
  • Vaclová, Tereza
  • Ferreira, Sofia
  • Urioste, Miguel
  • INGLADA PEREZ, LUCIA
  • Soberón, Nora
  • Blasco, Maria A.
  • Osorio, Ana
  • Benitez, Javier

publication date

  • March 2016

start page

  • 25815

end page

  • 25825

International Standard Serial Number (ISSN)

  • 1949-2553

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. J.B.'s laboratory is partially funded by the Spanish
    Ministry of Health PI12/00070 supported by FEDER
    funds, and the Spanish Research Network on Rare
    diseases (CIBERER). C.B-B is granted by the PI12/00070.
    M.A.B.'s laboratory is funded with the Spanish Ministry
    of Science and Innovation, projects SAF2008-05384 and
    2007-A-200950 (TELOMARKER), European Research
    Council Advanced grant GA#232854, the Körber
    Foundation, Fundación Botín and Fundación Lilly. MU is
    supported by the Spanish Ministry of Health PI14/00459
    with FEDER funds.