Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapy

Radiat Oncol. 2012 Apr 26;7:65. doi: 10.1186/1748-717X-7-65.

Abstract

Purpose: To examine the association of polymorphisms in ATM (codon 158), GSTP1 (codon 105), SOD2 (codon 16), TGFB1 (position -509), XPD (codon 751), and XRCC1 (codon 399) with the risk of severe erythema after breast conserving radiotherapy.

Methods and materials: Retrospective analysis of 83 breast cancer patients treated with breast conserving radiotherapy. A total dose of 50.4 Gy was administered, applying 1.8 Gy/fraction within 42 days. Erythema was evaluated according to the Radiation Therapy Oncology Group (RTOG) score. DNA was extracted from blood samples and polymorphisms were determined using either the Polymerase Chain Reaction based Restriction-Fragment-Length-Polymorphism (PCR-RFL) technique or Matrix-Assisted-Laser-Desorption/Ionization -Time-Of-Flight-Mass-Spectrometry (MALDI-TOF). Relative excess heterozygosity (REH) was investigated to check compatibility of genotype frequencies with Hardy-Weinberg equilibrium (HWE). In addition, p-values from the standard exact HWE lack of fit test were calculated using 100,000 permutations. HWE analyses were performed using R.

Results: Fifty-six percent (46/83) of all patients developed erythema of grade 2 or 3, with this risk being higher for patients with large breast volume (odds ratio, OR = 2.55, 95% confidence interval, CI: 1.03-6.31, p = 0.041). No significant association between SNPs and risk of erythema was found when all patients were considered. However, in patients with small breast volume the TGFB1 SNP was associated with erythema (p = 0.028), whereas the SNP in XPD showed an association in patients with large breast volume (p = 0.046). A risk score based on all risk alleles was neither significant in all patients nor in patients with small or large breast volume. Risk alleles of most SNPs were different compared to a previously identified risk profile for fibrosis.

Conclusions: The genetic risk profile for erythema appears to be different for patients with small and larger breast volume. This risk profile seems to be specific for erythema as compared to a risk profile for fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Ataxia Telangiectasia Mutated Proteins
  • Breast Neoplasms / genetics
  • Breast Neoplasms / radiotherapy*
  • Carcinoma / genetics
  • Carcinoma / radiotherapy*
  • Cell Cycle Proteins / genetics
  • DNA-Binding Proteins / genetics
  • Erythema / etiology
  • Erythema / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Glutathione S-Transferase pi / genetics
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide* / physiology
  • Protein-Serine-Threonine Kinases / genetics
  • Radiation Injuries / etiology
  • Radiation Injuries / genetics*
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Superoxide Dismutase / genetics
  • Transforming Growth Factor beta1 / genetics
  • Tumor Suppressor Proteins / genetics
  • X-ray Repair Cross Complementing Protein 1
  • Xeroderma Pigmentosum Group D Protein / genetics

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Tumor Suppressor Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Superoxide Dismutase
  • superoxide dismutase 2
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human