Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
DNA Cell Biol. 2010 Jul;29(7):349-56. doi: 10.1089/dna.2009.0982.
Perturbations in the cell cycle and apoptotic genes have been implicated in human malignancies. Cell cycle (MDM2 and Cyclin D1) and apoptotic (Fas) genes that are differentially expressed in urinary bladder cancer (UBC) were investigated with the susceptibility to UBC in northern India. A total of 212 UBC patients and age- and sex-matched 250 controls were investigated for MDM2 G309T, Cyclin D1 G870A, and Fas A670G polymorphisms by polymerase chain reaction and restriction fragment length polymorphism. MDM2 309GG was at reduced risk for developing UBC when compared with TT genotype (p = 0.027; odds ratio, 0.55). GG genotype was also associated with reduced risk in nonmuscle invasive bladder cancer (NMIBC) and muscle invasive BC (p = 0.006 and p = 0.049). Cyclin D1 AA genotype was associated with high risk in NMIBC (intermediate risk) stage (p = 0.015; odds ratio, 4.55). MDM2-Cyclin D1 interaction revealed overall protective effect. The GG genotype of MDM2 also showed a protective effect and high recurrence-free survival in Bacillus Calmette-Guerin-treated NMIBC patients (log rank p = 0.008). MDM2 GG genotype had protective effect and MDM2T309G polymorphism had profound influence in Bacillus Calmette-Guerin-treated UBC patients in the North Indian population.
细胞周期和凋亡基因的紊乱与人类恶性肿瘤有关。我们调查了印度北部膀胱癌（UBC）中差异表达的细胞周期（MDM2 和 Cyclin D1）和凋亡（Fas）基因，以探讨其与 UBC 的易感性。共对 212 例 UBC 患者和年龄及性别匹配的 250 例对照者进行了 MDM2 G309T、Cyclin D1 G870A 和 Fas A670G 多态性的聚合酶链反应和限制性片段长度多态性分析。与 TT 基因型相比，MDM2 309GG 基因型发生 UBC 的风险降低（p=0.027；比值比，0.55）。GG 基因型在非肌层浸润性膀胱癌（NMIBC）和肌层浸润性膀胱癌（BC）中也与较低的发病风险相关（p=0.006 和 p=0.049）。Cyclin D1 AA 基因型与 NMIBC（中危）分期的高风险相关（p=0.015；比值比，4.55）。MDM2-Cyclin D1 相互作用显示出总体保护作用。MDM2 的 GG 基因型也对卡介苗治疗的 NMIBC 患者具有保护作用和高无复发生存率（对数秩检验，p=0.008）。在印度北部人群中，MDM2 GG 基因型具有保护作用，并且 MDM2T309G 多态性对卡介苗治疗的 UBC 患者有显著影响。
