[XRCC1 and XPD genetic polymorphisms predict clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer].
OBJECTIVE
DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).


METHODS
XRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses.


RESULTS
The overall response rate (CR + PR) was 36.0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype (adjusted OR, 2.48; 95% CI, 1.36 - 4.51, P = 0.003). However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant (P = 0.004).


CONCLUSIONS
Those results suggest that the XRCC1 Arg194Trp and XPD Lys751Gln genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.
Yuan
Peng
P
Department of Medical Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Miao
Xiao-ping
XP
Zhang
Xue-mei
XM
Wang
Zhong-hua
ZH
Tan
Wen
W
Sun
Yan
Y
Zhang
Xiang-ru
XR
Xu
Bing-he
BH
Lin
Dong-xin
DX
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; D002945:Cisplatin / Q000008:administration & dosage; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D012074:Remission Induction; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D014747:Vinblastine; D016190:Carboplatin; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine