Polymorphisms in the DNA repair gene XRCC1 and survival of non-small cell lung cancer

Abstract

9585 Background: X-ray cross-complementing group 1 (XRCC1) protein is known to be mainly involved in BER(base excision repair) of DNA repair process. We investigated the association of three polymorphisms (codon 194, 280, and 399) of XRCC1 with lung cancer, whether these polymorphisms have an effect on survival of lung cancer patients received radiotherapy. Methods: 229 lung cancer patients with NSCLC in stage I-IV were recruited at Asan Medical Center and followed up at least every 3 months from the time of study entry. Genotyping was performed by single base primer exclusion assay using SNapShot Kit with blood samples from all patients. Kaplan-Meier survival curve was used for polymorphism effect on progression-free and overall survival. Hazard ratio by Cox-proportional hazard regression was calculated after adjustment for age, gender, histology, stage, and alcohol consumption. These variables were selected through the univariate analysis performed previously. The haplotype of XRCC1 polymorphisms was estimated by PHASE version 2.1. Results: The subjects were consisted of 191(83.4%) males and 38(16.6%) females. The median age was 62 (range 26 - 88) and 60% of patients were included in stage I-IIIa. More than 85% of patients had squamous cell carcinoma and adenocarcinoma. The mean survival time was 20.2 months and 22.5 months in progression-free and overall survival, respectively. XRCC1 codon 194, histology, and stage were shown to be a significant predictor in progression-free survival and alcohol consumption seemed to have protective effect significantly (p=0.028). The six haplotypes among XRCC1 polymorphisms (194, 280, and 399) were estimated by PHASE v.2.1. The patients with the haplotype pairs other than homozygous TGG haplotype pairs seemed to survive longer significantly compared with those with them (p=0.04). Conclusions: In the present study, we suggest that polymorphisms of XRCC1 have an effect on survival of lung cancer patients treated with radiotherapy and the effect appears more strongly considering haplotype pairs. No significant financial relationships to disclose.