Association ofp53codon 72 polymorphism andMDM2SNP309 with clinical outcome of advanced nonsmall cell lung cancer
| Autor: | Jin Soo Lee, Dae Ho Jang, Sung Young Lee, Geon Kook Lee, Ji-Youn Han |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Polymorphism Single Nucleotide Carcinoma Non-Small-Cell Lung Internal medicine Genotype Humans Medicine Codon Lung cancer Aged Aged 80 and over Polymorphism Genetic Performance status business.industry Proportional hazards model Hazard ratio Cancer Proto-Oncogene Proteins c-mdm2 Middle Aged Genes p53 medicine.disease Irinotecan Regimen Treatment Outcome Cancer research Female Tumor Suppressor Protein p53 business medicine.drug |
| Zdroj: | Cancer. 113:799-807 |
| ISSN: | 1097-0142 0008-543X |
| DOI: | 10.1002/cncr.23668 |
| Popis: | BACKGROUND. The purpose of the study was to investigate whether polymorphisms of p53 codon 72 (Arg72Pro) and MDM2 SNP309 (309T>G) affect p53 expression and the clinical outcome of patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. A total of 148 NSCLC patients, previously enrolled in 2 different prospective clinical trials, were genotyped for the p53 Arg72Pro and MDM2 309T>G polymorphisms. Immunohistochemical staining of p53 protein was performed on 61 tumor samples. Genotypes were correlated with p53 expression, clinicopathologic factors, tumor response, and survival. Multivariate logistic or Cox regression analyses were used to adjust for possible confounding variables. RESULTS. The distribution of sex, age, performance status, stage, tumor histology, and smoking habit was not significantly different among polymorphism variants. However, a significant association was observed between p53 Arg72Pro polymorphism and primary resistance to chemotherapy. Patients with the Pro/Pro variant were more likely to be resistant to first-line chemotherapy, especially the irinotecan plus cisplatin regimen, than those with Arg/Arg or Arg/Pro variants (60% vs 27%, P = .014). In multivariate analysis, the Pro/Pro genotype was strongly predictive for shorter progression-free survival (PFS) (hazard ratio [HR] = 1.952, P = .01). The p53 overexpression was associated with MDM2 SNP309. The TT genotype showed more p53 overexpression than TG or GG genotypes (P = .036). In multivariate analysis, the MDM2 TT genotype was independently predictive for longer survival (HR = 1.742, P = .032). CONCLUSIONS. The p53 72Pro/Pro variant was predictive for primary resistance to chemotherapy and shorter progression-free survival. The MDM2 SNP309 was associated with less p53 overexpression and prognostic for worse survival. Genotyping these polymorphisms may be useful for predicting the clinical outcome of advanced NSCLC. Cancer 2008. © 2008 American Cancer Society. |
| Databáze: | OpenAIRE |
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