[Polymorphisms in nucleotide excision repair genes XPC and XPD and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer].
OBJECTIVE
Nucleotide excision repair has been shown to have great impact on the sensitivity of tumors to platinum-based chemotherapy. This study was to examine the association between genetic polymorphisms in XPC and XPD, two important components in nucleotide excision repair system, and clinical response to platinum-based chemotherapy in advanced non-small cell lung cancer.


METHODS
Patients (n = 151) treated with platinum-based chemotherapy were genotyped for the AT dinucleotide insertion or deletion in intron 9 of XPC or Lys751Gln polymorphism in XPD. Clinical response to chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model and adjusted for sex, age, clinical stage, and regime of chemotherapy.


RESULTS
The overall response rate to the chemotherapy (CR + PR) was 35.1%, with 1 CR, 52 PR, 75 SD, and 23 PD. It was found that patients with the XPC LL genotype had significantly higher response rate than patients with the XPC SS genotype (adjusted OR = 3.19, 95% CI = 1.11 - 9.17; P = 0.031). However, no association was found between the XPD Lys751Gln polymorphism and response to the chemotherapy. In addition, these two polymorphisms seemed to have synergic effect, with the OR being 2.90 (95% CI = 1.07 - 7.86) for patients carrying the XPC LL and XPD Lys/Lys genotypes compared with those carrying the XPC SS or SL and XPD Lys/Lys genotypes.


CONCLUSIONS
These results suggest that genetic polymorphisms in nucleotide excision repair might be associated with clinical response to platinum-based chemotherapy.
Yuan
Peng
P
Department of Medical Oncology, Cancer Hospital & Institute, Chinese Academy of Medical Sciences, 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
Xu
Bing-he
BH
Lin
Dong-xin
DX
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; 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; D010984:Platinum / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D004268:DNA-Binding Proteins; C086984:XPC protein, human; D010984:Platinum; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin