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

authors

  • Benitez Buelga, Carlos
  • Vaclov√°, Tereza
  • Ferreira, Sofia
  • Urioste, Miguel
  • INGLADA PEREZ, LUCIA
  • Sober√≥n, Nora
  • Blasco, Maria A.
  • Osorio, Ana
  • Benitez, Javier

publication date

  • March 2016

start page

  • 25815

end page

  • 25825

issue

  • 18

volume

  • 7

Electronic International Standard Serial Number (EISSN)

  • 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 resent 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.

subjects

  • Biology and Biomedicine

keywords

  • brca1 and brca2; telomere shortening; ogg1 polymorfism; cancer risk modifier; dna damage