Department of Urology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
Cancer Sci. 2009 Dec;100(12):2376-82. doi: 10.1111/j.1349-7006.2009.01331.x. Epub 2009 Aug 27.
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.
铂类为基础的放化疗（CRT）作为膀胱保存治疗，已显示出在肌层浸润性膀胱癌中具有有希望的结果。然而，由于某些非反应性膀胱肿瘤患者的膀胱切除术延迟，CRT 可能会降低生存率。因为 p53 肿瘤抑制途径，包括其 MDM2 对应物，在化疗和放疗相关的影响中非常重要，TP53 和 MDM2 基因中的功能性多态性可能会影响对治疗的反应和 CRT 后的预后。我们研究了两种此类多态性，以及 p53 过表达，与接受 CRT 治疗的膀胱癌患者的反应或生存之间的关系。该研究组包括 96 名接受过 CRT 治疗的膀胱癌患者。使用 PCR-RFLP 对 TP53（密码子 72，精氨酸>脯氨酸）和 MDM2（SNP309，T>G）中的单核苷酸多态性（SNP）进行基因分型，并使用免疫组织化学法检测 p53 的核表达水平。没有一个基因型或 p53 过表达与 CRT 的反应明显相关。然而，MDM2 T / G + G / G 基因型的患者在 CRT 后癌症特异性生存率提高（P = 0.009）。在多变量分析中，MDM2 T / G + G / G 基因型，以及 TP53 和 MDM2 中的总变异等位基因超过两个，与改善的癌症特异性生存率独立相关（P = 0.031 和 P = 0.015）。此外，MDM2 基因型与免于行膀胱切除术的生存时间显著相关（P = 0.030）。这些结果表明，TP53 和 MDM2 基因型可能是膀胱癌 CRT 后有用的预后因素，有助于患者选择膀胱保存治疗。
