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

Abstract

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.

Keywords:

• Radiotherapy
• radiation-induced fibrosis
• single nucleotide polymorphisms
• formalin fixed paraffin embedded tissue samples

Acronyms
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;
APEX	=	apurinic/apyrimidinic exonuclease gene;
ATM	=	gene of ataxia telangiectasia mutated

Acronyms
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;
APEX	=	apurinic/apyrimidinic exonuclease gene;
ATM	=	gene of ataxia telangiectasia mutated