[Single nucleotide polymorphisms in XRCC1 and clinical response to platin-based chemotherapy in advanced non-small cell lung cancer].
OBJECTIVE
DNA repair capacity correlated with sensitivity of cancer cells towards platin-based chemotherapy. This study examined the association between genetic polymorphisms of DNA repair gene XRCC1 and response to cisplatin- or carboplatin-based chemotherapy of advanced non-small cell lung cancer (NSCLC).


METHODS
Totally 105 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin-based chemotherapy, and clinical response was evaluated after 2 to 3 cycles. XRCC1 genotypes were determined by PCR-RFLP methods using DNA samples isolated from peripheral blood collected before treatment. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression.


RESULTS
The response rate to the chemotherapy in patients with the 194Arg/Trp or Trp/Trp genotype significantly higher than that in patients with the Arg/Arg genotype (43.1% vs. 20.3%;OR=2.97,95% CI=1.15-7.72;P< 0.05). The response rate to chemotherapy was also significantly higher in patients with the 399Arg/Arg genotype than that in patient with the Arg/Gln or Gln/Gln genotype (41.5% vs. 21.2%;OR=2.65,95% CI=1.03-6.87;P< 0.05).Furthermore, it appeared that 194Arg/Trp and 399Arg/Arg genotypes had synergic effect on the chemotherapy efficacy. Patients with both of these two polymorphisms had a response rate of 66.7% which was significantly greater than that in patients with other genotypes (response rate ranging from 20.0% to 23.1%, P< 0.001).


CONCLUSIONS
Polymorphisms in the XRCC1 gene may have significant impact on the response of NSCLC patients to platin-based chemotherapy.
Department of Medical Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China. dlin@public.bta.net.cn
Zhong-Hua
ZH
Wang
Xiao-Ping
XP
Miao
Wen
W
Tan
Xiang-Ru
XR
Zhang
Bing-He
BH
Xu
Dong-Xin
DX
Lin
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D043823:Taxoids / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D043823:Taxoids; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000077143:Docetaxel; D014747:Vinblastine; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine