Department of Otolaryngology-Head and Neck Surgery, The second affected hospital to Nanchang University, Nanchang, China.
BMC Cancer. 2010 Apr 18;10:147. doi: 10.1186/1471-2407-10-147.
The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.
In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP.
We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58).
The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC.
抑癌基因 TP53 及其负调控因子 MDM2 在肿瘤发生中起着关键作用。先前的病例对照研究也表明 TP53 72Arg>Pro 和 MDM2 309T>G 多态性与常见癌症的风险有关。然而,这两个功能多态性与鼻咽癌(NPC)易感性之间的关系尚未被探索。
在这项研究中,我们在中国人群中进行了病例对照研究,共纳入了 522 例 NPC 患者和 722 例健康对照者,采用 PCR-RFLP 技术进行分析。
我们发现 MDM2 GG(比值比 [OR] = 2.83,95%置信区间 [CI] = 2.08-3.96)和 TG(OR = 1.49,95% CI = 1.16-2.06)基因型与 NPC 风险增加相关。与 Arg/Arg 基因型相比,TP53 Pro/Pro 基因型也与 NPC 风险增加相关(OR = 2.22,95% CI = 1.58-3.10)。MDM2 和 TP53 多态性的基因-基因相互作用以超过相乘的方式增加成人 NPC 风险(同时存在 MDM2 GG 和 TP53 Pro/Pro 基因型的 OR = 7.75,95% CI = 3.53-17.58)。
这些发现表明 MDM2 和 TP53 基因的多态性可能是 NPC 发生的遗传修饰因子。