[Correlation of genetic polymorphisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer patients to platinum-based chemotherapy].
OBJECTIVE
DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. This study was to examine the correlations of polymorphisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer (NSCLC) to platinum-based chemotherapy.


METHODS
Treatment outcomes of 200 advanced NSCLC patients, treated with platinum-based chemotherapy, were evaluated. XPC-PAT, XPD Lys751Gln (rs1052559), and ERCC1 C8092A (rs1052559) were genotyped by polymerase chain reaction-amplified fragment length polymorphism (PCR-AFLP) or PCR-restrictive fragment length polymorphism (PCR-RFLP) methods in the 200 patients. Unconditional logistic regression model was used to analyze the correlation of genetic polymorphisms to clinical response.


RESULTS
The distributions of XPC-PAT genotypes differed significantly between response group (complete response + partial response) and un-response group (stable disease + progressive disease)(P=0.023). The XPC LL genotype carriers had higher response rate than the SS genotype carriers (OR=3.04; 95% CI=1.25-7.41, P= 0.015). The XPD Lys751Gln and ERCC1 C8092A polymorphisms were not found to be associated with platinum-based chemotherapy. However, these 3 genetic polymorphisms in nucleotide excision repair system had interaction in the drug sensitivity (P=0.021).


CONCLUSIONS
The genetic polymorphisms of XPC-PAT, XPD Lys751Gln, and ERCC1 C8092A in nucleotide excision repair system may be associated with sensitivity of NSCLC patients to platinum-based chemotherapy.
Yuan
Peng
P
Department of Medical Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P. R. China.
Miao
Xiao-Ping
XP
Zhang
Xue-Mei
XM
Wang
Zhong-Hua
ZH
Tan
Wen
W
Zhang
Xiang-Ru
XR
Sun
Yan
Y
Xu
Bing-He
BH
Lin
Dong-Xin
DX
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D004268:DNA-Binding Proteins; C086984:XPC protein, human; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin