title: Effects of polymorphisms in the XRCC1, XRCC3, and XPG genes on clinical outcomes of platinum-based chemotherapy for treatment of non-small cell lung cancer.
abstract: This study aimed to investigate the effects of single-nucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPG His104Asp, and XPG His46His in genes involved in the DNA-repair pathway on the outcomes of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The study period was from January 2005 to January 2006, and 378 NSCLC patients were enrolled within 1 month after being diagnosed with NSCLC. Genomic DNA was extracted using the Qiagen Blood Kit. Polymerase chain reaction combined with a restriction fragment length polymorphism assay was used for genotyping. Individuals with the XRCC1 399A/A genotype had a higher probability of responding well to platinum-based chemotherapy, indicated by an odds ratio (OR) of 2.27 [95% confidence interval (CI)=1.64-6.97]. Similarly, the XPG T/T genotype was significantly associated with improved responses to chemotherapy, indicated by an OR of 1.90 (95%CI=1.10-3.28). The XRCC1 399A/A genotype was significantly associated with longer disease-free survival and overall survival, indicated by hazard ratios (HRs) of 0.48 (95%CI=0.25-0.88) and 0.51 (95%CI=0.26- 0.98), respectively. Moreover, the XPG 46T/T genotype increased the likelihood of longer disease-free survival and overall survival of NSCLC patients treated with platinum-based chemotherapy (HR=0.47; 95%CI=0.22-0.82 and HR=0.52; 95%CI=0.31- 0.96, respectively). These results indicate that XRCC1 Arg399Gln and XPG His46His might significantly affect the clinical outcomes of platinum-based chemotherapy, highlighting the need for larger studies to confirm the role of these two SNPs in outcomes of NSCLC treatments.
authors.affiliation: Beijing Chest Hospital, Beijing, China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Jin
authors.affiliation: Department of Cell Biology Research, Tuberculosis and Thoracic Tumour Research Institute, Beijing, China.
authors.forename: X T
authors.initials: XT
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology Research, Tuberculosis and Thoracic Tumour Research Institute, Beijing, China.
authors.forename: L N
authors.initials: LN
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology Research, Tuberculosis and Thoracic Tumour Research Institute, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Biology Research, Tuberculosis and Thoracic Tumour Research Institute, Beijing, China.
authors.forename: W T
authors.initials: WT
authors.lastname: Yue
authors.affiliation: Beijing Chest Hospital, Beijing, China shaofa_bch@163.com.
authors.forename: S F
authors.initials: SF
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D010984:Platinum / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D010984:Platinum; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D000099250:DNA Excision Repair Protein ERCC-5; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human