The role of base excision repair in pathogenesis of breast cancer in the Polish population

Mol Carcinog. 2016 Dec;55(12):1899-1914. doi: 10.1002/mc.22436. Epub 2015 Nov 19.

Abstract

Breast cancer (BC) is leading type of cancer among group of women, which determines almost 23% of invasive cancers. It has been reported repeatedly that the level of oxidative stress is higher for BC in comparison to cancer-free woman. The goal of the present study was to evaluate the role of base excision repair (BER) pathway in the development of BC. One-hundred seventy-one women with confirmed BC and 222 healthy controls were enrolled in presented study. The level of oxidative DNA damage and the kinetic of their repair were analyzed by the modified alkaline comet assay. The efficiency of BER pathway was evaluated by BER assay. The presence of the 326Cys/Cys genotype and 326Cys allele of OGG1 gene and the 324His/His of MUTYH gene are associated with increased risk of BC development. Moreover, correlation between clinical parameter with selected genes has shown increased risk of BC progression. The survival analysis has shown a significant lower DFS for individuals with the 762Ala/Ala genotype compared to 762Val/Vla carriers and the 762Val/Ala genotype in relation to concomitant chemotherapy and radiotherapy. In subgroup of patients with alone chemotherapy and alone radiotherapy, the 762Val/Val genotype was significantly associated with lower overall survival. Furthermore, we also elevated the level of basal and oxidative DNA damage in a group of patients with BC in relation to healthy controls. We also observed the difference in effectiveness of DNA damage repair. The results of present studies suggested the important role of BER pathway in BC development. © 2015 Wiley Periodicals, Inc.

Keywords: base excision repair; breast cancer; oxidative DNA damage; oxidative stress; polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast / metabolism
  • Breast / pathology*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • DNA Damage
  • DNA Glycosylases / genetics
  • DNA Repair*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Poland / epidemiology
  • Poly (ADP-Ribose) Polymerase-1 / genetics
  • Polymorphism, Single Nucleotide
  • Risk Factors

Substances

  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • DNA Glycosylases
  • mutY adenine glycosylase
  • oxoguanine glycosylase 1, human