ABSTRACT
The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death,which may be associated with the development of chronic obstructive pulmonary disease (COPD).However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 (XRCC1), a base exci-sion repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 (Arg399Gln) and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restrietion fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg geno-type, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype (adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028); after stratifying by smoking exposure, in light smokers, com-pared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype (adjusted OR=0.39, 95% CI 0.16-0.94,P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively). In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.
ABSTRACT
Objective To investigate whether the single nucleotide polymorphisms (SNP) in DNA repair gene XRCC1(X-ray repair cross-complementing 1) were associated with the survival of cisplatin based combination concurrent chemoradiotherapy in esophagus cancer. Methods Overall 286 esophagus cancer patients receiving cisplatinum based chemotherapy were investigated. 5' nuclease allelic discrimination assay (TaqMan) and real-time PCR were taken to assess XRCC1 genotypes. Efficacies and adverse-effects were analyzed individually according to their genotype. Results Short-time effects showed the RR rate in patients with Arg/Arg and Arg/GIn genotypes(A group) was 93.56 %, significantly higher than 69.81% (P<0.05) in patients with GIn/GIn genotype (B group). The 1-year and 3-year survival rates were 82.8 %, 41.2 % in A group, significantly (P<0.05) different from 58.5 %, 26.4 % in B group, respectively. No statistically differences were found on adverse effects. Conclusion Significant relationships are found between single nucleotide polymorphisms in XRCC1 and outcome in esophagus cancer receiving cisplatin based concurrent chemoradiotherapy.