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.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Andreassen
C N
CN
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. nicolaj@oncology.dk
Alsner
J
J
Overgaard
M
M
Sørensen
F B
FB
Overgaard
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000532:radiotherapy / Q000601:surgery; D018797:Cell Cycle Proteins / Q000235:genetics*; D015331:Cohort Studies; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005355:Fibrosis / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D016612:Paraffin Embedding; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011832:Radiation Injuries / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D040521:Subcutaneous Tissue / Q000473:pathology* / Q000528:radiation effects*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004247:DNA