TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin

Abstract

Purpose : The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with advanced gastric cancer. Patients and methods : Fifty-seven patients with advanced gastric cancer treated with paclitaxel and cisplatin combination chemotherapy were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue, and the single nucleotide polymorphisms (SNPs) of ten apoptosis-related genes [LTA, TP53, BCL2L11, BID, FASL, caspase 3, caspase 6, caspase 7, and caspase 9] determined using a polymerase chain reaction–restriction fragment length polymorphism assay. Results : The Arg/Pro and Pro/Pro genotypes of TP53 codon 72 were significantly correlated with a lower response rate to the combination chemotherapy when compared to the Arg/Arg genotype (35.7 vs. 66.7%, P-value 0.019) in a logistic regression analysis. A multivariate survival analysis also showed that the time to progression for the patients with the Arg/Pro and Pro/Pro genotypes of TP53 codon 72 was worse than for the patients with the Arg/Arg genotype (Hazard ratio = 3.056, P-value = 0.047), whereas the overall survival was not significantly different. Conclusion : The TP53 codon 72 SNP was found to be predictive of the response to chemotherapy and correlate with the time to progression in patients with advanced gastric cancer treated with paclitaxel and cisplatin chemotherapy. Keywords : Gastric cancer – Chemotherapy – TP53 – Polymorphism