Polymorphisms of DNA Repair Gene XRCC1 and Radiation Sensitivity

ABSTRACT

PURPOSE: The goal of this study was to find lung cancer-related single nucleotide polymorphisms (SNP) and define their association with clinical results. Material and Methods: One hundred and thirty-six non-small cell lung cancer patients, who received radiotherapy at the Asan Medical Center, were recruited between August 2002 and September 2003. Demographic and clinical informations were obtained from a self-administered questionnaire and from the subject's medical records, respectively. Blood samples were collected from all study subjects at the time of enrollment. Genomic DNA was extracted from peripheral blood lymphocytes using a QIAamp DNA Blood Mini Kit. TaqMan assay, denaturing HPLC and single base pair primer extension assay using SNaPshot kits were employed as the SNP screening techniques. The candidate SNP for screening was XRCC1-R399Q. RESULTS: Patients carrying the 399Gln variant allele had a significantly longer progression-free survival than those with the 399Arg homozygote in tumor stages I-IIIa (p=0.005). In the Cox-proportional hazards model, the XRCC1 codon 399 polymorphism was a statistically significant predictor for progression-free survival in tumor stages I-IIIa (p=0.03). CONCLUSION: The use of molecular predictors of the progression-free survival in non-small cell lung cancer patients, particularly at stages I-IIIa, may provide important criteria for prognosis of the patients undergoing radiotherapy. However, there is still a need for further study to establish the role of these polymorphisms as useful predictors