title: Association of TP53 and MDM2 polymorphisms with survival in bladder cancer patients treated with chemoradiotherapy.
abstract: Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, CRT might diminish survival as a result of the delay in cystectomy for some patients with non-responding bladder tumors. Because the p53 tumor suppression pathway, including its MDM2 counterpart, is important in chemotherapy- and radiotherapy-associated effects, functional polymorphisms in the TP53 and MDM2 genes could influence the response to treatment and the prognosis following CRT. We investigated associations between two such polymorphisms, and p53 overexpression, and response or survival in bladder cancer patients treated with CRT. The study group comprised 96 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms (SNPs) in TP53 (codon 72, arginine > proline) and MDM2 (SNP309, T > G) were genotyped using PCR-RFLP, and nuclear expression levels of p53 were examined using immunohistochemistry. None of the genotypes or p53 overexpression was significantly associated with response to CRT. However, patients with MDM2 T / G + G / G genotypes had improved cancer-specific survival rates after CRT (P = 0.009). In multivariate analysis, the MDM2 T / G + G / G genotypes, and more than two of total variant alleles in TP53 and MDM2, were independently associated with improved cancer-specific survival (P = 0.031 and P = 0.015, respectively). In addition, MDM2 genotypes were significantly associated with cystectomy-free survival (P = 0.030). These results suggest that the TP53 and MDM2 genotypes might be useful prognostic factors following CRT in bladder cancer, helping patient selection for bladder conservation therapy.
authors.affiliation: Department of Urology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Asano
authors.initials: A
authors.lastname: Shinohara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.forename: Jun
authors.initials: J
authors.lastname: Nishijima
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kawai
authors.forename: Taku
authors.initials: T
authors.lastname: Misumi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagao
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003062:Codon; D003131:Combined Modality Therapy; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2