Polymorphic Variants in Oxidative Stress Genes and Acute Toxicity in Breast Cancer Patients Receiving Radiotherapy

Cancer Res Treat. 2016 Jul;48(3):948-54. doi: 10.4143/crt.2015.360. Epub 2016 Jan 14.


Purpose: Reactive oxygen species (ROS) are generated as an indirect product of radiation therapy (RT). Genetic variation in genes related to ROS metabolism may influence the level of RT-induced adverse effects. We evaluated the potential association of single nucleotide polymorphism (SNP)-related response to radiotherapy injury in breast cancer patients undergoing RT.

Materials and methods: Eighty patients receiving conventional RT were included. Acute effects were evaluated according to the Radiation Therapy Oncology Group (RTOG) scores. DNA was extracted from blood and buccal swab samples. SNPs were genotyped for GSTP1, GSTA1, SOD2, and NOS3 genes by polymerase chain reaction-based restriction fragment length polymorphism. Univariate analysis (odds ratios [ORs] and 95% confidence interval [CI]) and principal component analysis were used for correlation of SNPs and factors related to risk of developing ≥ grade 2 acute effects.

Results: Sixty-five patients (81.2%) showed side effects, 32 (40%) presented moderate to severe acute skin toxicity, and 33 (41.2%) manifested minimal acute skin reactions by the end of treatment. In both univariate and multivariate analyses, nominally significant associations were found among body mass index (OR, 3.14; 95% CI, 8.5338 to 1.1274; p=0.022), breast size (OR, 5.11; 95% CI, 17.04 to 1.54; p=0.004), and grade ≥ 2 acute radiation skin toxicity. A significant association was also observed between NOS3 G894T polymorphism (OR, 9.8; 95% CI, 211.6 to 0.45; p=0.041) and grade ≥ 2 acute radiation skin toxicity in patients with neo-adjuvant chemotherapy treatment.

Conclusion: The analysis of the factors involved in individual radiosensitivity contributed to the understanding of the mechanisms underlying this trait.

Keywords: Acute toxicity; Breast neoplasm; Oxidative stress; Radiation tolerance; Radiotherapy; Single nucleotide polymorphism.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Amplified Fragment Length Polymorphism Analysis
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / radiotherapy*
  • Female
  • Genotype
  • Genotyping Techniques / methods
  • Glutathione S-Transferase pi / genetics
  • Glutathione Transferase / genetics
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / adverse effects
  • Neoadjuvant Therapy / methods
  • Nitric Oxide Synthase Type III / genetics
  • Odds Ratio
  • Oxidative Stress / genetics*
  • Polymorphism, Restriction Fragment Length / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Prospective Studies
  • Radiation Injuries / genetics*
  • Radiation Tolerance / genetics*
  • Reactive Oxygen Species / metabolism*
  • Reactive Oxygen Species / radiation effects
  • Risk Factors
  • Sequence Analysis, DNA
  • Skin / radiation effects
  • Superoxide Dismutase / genetics


  • Reactive Oxygen Species
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • superoxide dismutase 2
  • GSTA1 protein, human
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase