TP53 codon 72 single nucleotide polymorphism (SNP) in gemcitabine (gem)/cisplatin (cis)-treated non-small-cell lung cancer (NSCLC) patients (p)

Abstract

7161 Background: TP53 occupies a central role in mediating cellular responses to genotoxic insults through its effects on gene transcription and DNA synthesis and repair. The codon 72 SNP in exon 4, carried by 20–40% of the population, leads to an arginine to proline substitution (G-C transversion). We hypothesized that CC homozyogtes and C-carriers (heterozygotes) could have better response and survival Methods: 202 stage IV NSCLC p were included from August 2001 to July 2002. TaqMan 5' nuclease assay was used to examine TP53 72 SNP from baseline peripheral blood lymphocytes. Results:: p characteristics: median age: 61; 91% male; PS 0: 23.4%, 1: 62.7%, 2: 13.9%; adenocarcinoma: 43.1%, pleural effusion: 16%. Overall: response rate (RR) 38.6%; time to progression (TTP) 6 months (m); median survival (MS) 10.56 m. TP53 72 genotypes: GG 60.4%; GC 34.4%; CC 5.2%. By genotype: RR: GG 43%, GC: 38.5%, CC 40%; TTP: GG 6 m, GC 5.8 m, CC 8.7 m; MS: GG 9.8 m, GC 12.3 m, CC 10.5 m. For p with extrapulmonary metastases, those with PS 0 had a lower risk of progression than those with PS 1 (hazard ratio = 0.4; P=0.006); TTP 8.7 m vs 4.4 m (P=0.007). Such differences were not found for p with pulmonary metastases Conclusions: Although TP53 72 SNP was an attractive candidate marker for chemotherapy outcome, our results provide little support for this hypothesis. Intriguingly, among p with good PS, those with extrapulmonary metastases and PS 0 had significantly better outcome than those with PS 1. No significant financial relationships to disclose.