Risk of radiation-induced subcutaneous fibrosis in relation to single nucleotide polymorphisms in TGFB1, SOD2, XRCC1, XRCC3, APEX and ATM--a study based on DNA from formalin fixed paraffin embedded tissue samples

Int J Radiat Biol. 2006 Aug;82(8):577-86. doi: 10.1080/09553000600876637.


Purpose: In two previously published studies, associations with risk of radiation-induced subcutaneous fibrosis were found for single nucleotide polymorphisms (SNP) in TGFB1 (transforming growth factor beta 1 gene), XRCC1 (X-ray repair cross-complementing 1 gene), XRCC3 (X-ray repair cross-complementing 3 gene), SOD2 (manganese superoxide dismutase gene) and ATM (gene of ataxia telangiectasia mutated). The present study was conducted to seek a confirmation of these findings.

Materials and methods: Like the 41 patients previously investigated, the 120 subjects included in the present study were accrued from a historical cohort of 319 post-mastectomy radiotherapy patients. All patients received hypo-fractionated radiotherapy. The TGFB1 position--509, codons 10 and 25, XRCC1 codons 194, 280 and 399, XRCC3 codon 241, SOD2 codon 16, ATM codon 1853 and APEX (apurinic/apyrimidinic exonuclease gene) codon 148 polymorphisms were assessed based on archival histological material. Differences in fibrosis risk were quantified from dose-response assessments.

Results: For none of the investigated polymorphisms, significant associations with risk of subcutaneous fibrosis were observed. A detailed analysis did not reveal any obvious explanation for the discrepancy between the previous and the present study.

Conclusion: The previously observed associations with risk of radiation-induced subcutaneous fibrosis could not be replicated in the present study. Further studies are needed to elucidate the influence of genetic variation upon normal tissue radiosensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • Cell Cycle Proteins / genetics*
  • Cohort Studies
  • DNA / genetics
  • DNA / radiation effects
  • DNA-Binding Proteins / genetics*
  • Dose-Response Relationship, Radiation
  • Female
  • Fibrosis / genetics
  • Humans
  • Middle Aged
  • Paraffin Embedding
  • Polymorphism, Single Nucleotide / genetics
  • Radiation Injuries / genetics*
  • Radiotherapy / adverse effects*
  • Risk Assessment / methods
  • Risk Factors
  • Subcutaneous Tissue / pathology*
  • Subcutaneous Tissue / radiation effects*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • DNA