[Association of the responsiveness of advanced non-small cell lung cancer to platinum-based chemotherapy with p53 and p73 polymorphisms].
OBJECTIVE
It has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).


METHODS
A total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro-->Arg and p73 exon 2 G4C14-->A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the 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. All statistical tests were two-sided.


RESULTS
The p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively.


CONCLUSIONS
Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.
Yuan
Peng
P
Department of Medical Oncology, Cancer 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
Zhang
Xiang-ru
XR
Sun
Yan
Y
Xu
Bing-he
BH
Lin
Dong-xin
DX
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / 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*; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D017239:Paclitaxel / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin