Decreased DNA repair gene XRCC1 expression is associated with radiotherapy-induced acute side effects in breast cancer patients

Gene. 2016 May 10;582(1):33-7. doi: 10.1016/j.gene.2016.01.040. Epub 2016 Jan 27.

Abstract

DNA repair plays a critical role in response to ionizing radiation (IR) and developing of radiotherapy induced normal tissue reactions. In our study, we investigated the association of radiotherapy related acute side effects, with X-ray repair cross complementing group 1 (XRCC1) and Poly (ADP-ribose) polymerase 1 (PARP1) DNA repair gene expression levels, their changes in protein expression and DNA damage levels in breast cancer patients. The study included 40 women with newly diagnosed breast cancer; an experimental case group (n=20) with acute side effects and the control group (n=20) without side effects. For gene and protein expression analysis, lymphocytes were cultured for 72 h and followed by in vitro 2 Gray (Gy) gamma-irradiation. For detection of DNA damage levels, lymphocytes were irradiated with in vitro 2 Gy gamma-rays and followed by incubation for 72 h. XRCC1 mRNA and protein expression levels were significantly higher in controls than in experimental cases (P=0.020). In terms of DNA damage levels, an increased frequency of micronucleus (MN) was observed in experimental cases versus controls, but this association was not significant (P=0.206). We also observed a significant negative correlation between MN frequency and XRCC1 protein levels in experimental (r=-0.469, P=0.037) vs control (r=-0.734, P<0.001). Our results suggested that decreased XRCC1 expression levels might be associated with the increased risk of therapeutic IR-related acute side effects in patients with breast cancer.

Keywords: Acute side effects; DNA damage; DNA repair; XRCC1; breast cancer; radiation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • DNA Damage / radiation effects
  • DNA Repair / radiation effects
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Female
  • Gamma Rays / adverse effects
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / biosynthesis*
  • Poly(ADP-ribose) Polymerases / genetics
  • Radiotherapy / adverse effects
  • X-ray Repair Cross Complementing Protein 1

Substances

  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases