Association of the responsiveness of advanced non-small cell lung cancer to platinum-based chemotherapy with p53 and p73 polymorphisms
Yuan, P.; Miao, X-ping.; Zhang, X-mei.; Wang, Z-hua.; Tan, W.; Zhang, X-ru.; Sun, Y.; Xu, B-he.; Lin, D-xin.
Zhonghua Zhong Liu Za Zhi 28(2): 107-110
2006
ISSN/ISBN: 0253-3766 PMID: 16750013 Document Number: 601867
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/G4CI4 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. Conclusion Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.