Abstract C109: Association of TP53 gene polymorphism with response to platinum-based doublet chemotherapy in non-small cell lung cancer patients.

Abstract

Abstract Here we show that TP53 SNP is involved in chemotherapeutic responses in non-small cell lung cancer (NSCLC) patients. To identify polymorphisms in DNA repair genes that affect responses to platinum-based doublet chemotherapy, 640 NSCLC patients, who received platinum-based doublet chemotherapy and whose responses were evaluated by the Response Evaluation Criteria in Solid Tumors, were subjected to an association study between the response and genotypes for 30 SNPs in 27 DNA repair genes. Candidate SNPs were selected by screening of a discovery set of 201 cases and their associations were validated in an independent set of 439. Homozygotes for the TP53–72Pro allele of the TP53-Arg72Pro SNPs showed a better response rate (54.3%) than those for the TP53–72Arg allele (29.1%), and TP53–72Pro allele homozygotes had significantly longer progression-free and overall survivals than TP53–72Arg allele homozygotes. Minor allele carriers for a SNP, Lys940Arg, in the PARP1 (poly ADP-ribose polymerase 1) gene showed a better response rate to the regimen using paclitaxel (45.8%) than to the regimen using gemcitabine (10.5%). These results indicate that polymorphisms in the TP53 and PARP1 genes are involved in inter-individual differences in the response to platinum-based doublet chemotherapy in NSCLC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C109.