DNA repair capacity and acute radiotherapy adverse effects in Italian breast cancer patients.
Therapeutic exposure to ionising radiation can induce normal tissue side effects which consistently differ among individuals suggesting a possible genetic control. One approach to elucidate the underlying mechanisms is to analyse the relation between genetic traits, biomarkers of in vitro DNA damage and side toxicity in vivo. 43 breast cancer (BC) patients receiving radiotherapy after a breast-conserving surgery were recruited together with 34 age- and sex-matched healthy controls. Adverse tissue reactions were recorded as indicators of radiotherapy susceptibility. All blood samples from both patients (35) and controls (34) were irradiated in vitro and DNA primary damage and repair kinetic were measured through Comet assay. All study subjects were genotyped for XRCC1, OGG1 and XRCC3 gene polymorphisms. In our small groups we found a positive association between XRCC1 variant allele (399Gln) and the occurrence of breast cancer [p=0.01; OR=2.41, 95%CI (1.24-4.66)]. BC patients showed a higher degree of basal (p<0.001) and X-ray induced DNA damage (p<0.01) when compared to healthy controls. A reduced repair ability was found in BC patients showing high degrees of tissue side effects as classified by Radiation Morbidity Scoring Scheme. BC patients showed an impairment of their DNA repair capacity associated with the development of radiation sensitivity but not with polymorphisms in any of the considered genes.
Sterpone
Silvia
S
Department of Biology, University of Roma TRE, V.le G. Marconi 446, Rome 00146, Italy.
Cornetta
Tommaso
T
Padua
Luca
L
Mastellone
Valeria
V
Giammarino
Daniela
D
Testa
Antonella
A
Tirindelli
Donatella
D
Cozzi
Renata
R
Donato
Vittorio
V
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D008214:Lymphocytes / Q000648:ultrastructure*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011836:Radiation Tolerance / Q000235:genetics; D011878:Radiotherapy / Q000009:adverse effects*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human