Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Endocrinology, Zahedan University of Medical Sciences, Zahedan, Iran.
J Cell Physiol. 2019 Aug;234(8):12934-12940. doi: 10.1002/jcp.27960. Epub 2018 Dec 13.
Murine double minute clone 2 (MDM2) protein plays an important role in the regulation of p53 tumor suppressor. Genetic polymorphisms of the MDM2 gene are the candidate variants in susceptibility to various cancers. In the present study, we aimed to investigate the possible effects of MDM2 309T>G (rs2279744) and I/D (rs3730485) polymorphisms on papillary thyroid carcinoma (PTC) susceptibility and clinical or pathological features of the disease. A case control study was carried out involving in a total of 131 patients with PTC and 144 healthy controls. Both cases and controls were genotyped for MDM2 309T>G and I/D polymorphisms. There was no significant difference regarding MDM2 309T>G and I/D genotypes between patients with PTC and controls in neither dominant nor recessive and allelic models. The frequency of G-D haplotype was higher in patients with PTC and this haplotype was associated with a 1.7-fold increased risk of PTC. The MDM2 309T>G polymorphism was associated with a higher risk of III-IV stages in patients with PTC. The MDM2 ID genotype was significantly higher in patients with PTC less than 40 years and associated with larger tumor size (≥1 cm). In conclusion, the G-D haplotype but not MDM2 309T>G and I/D polymorphisms were associated with higher risk of PTC. MDM2 309T>G polymorphism was associated with a higher incidence of III-IV stages, however, I/D polymorphism was associated with larger tumor size and a lower age of disease occurrence.
鼠双微体 2 基因（MDM2）蛋白在调节 p53 肿瘤抑制因子方面发挥着重要作用。MDM2 基因的遗传多态性是各种癌症易感性的候选变异。本研究旨在探讨 MDM2 309T>G（rs2279744）和 I/D（rs3730485）多态性对甲状腺乳头状癌（PTC）易感性及疾病临床病理特征的可能影响。进行了一项病例对照研究，共纳入 131 例 PTC 患者和 144 例健康对照者。对所有研究对象进行 MDM2 309T>G 和 I/D 多态性的基因分型。无论是显性还是隐性和等位基因模型，PTC 患者与对照组之间 MDM2 309T>G 和 I/D 基因型均无显著差异。PTC 患者中 G-D 单倍型频率较高，该单倍型与 PTC 风险增加 1.7 倍相关。MDM2 309T>G 多态性与 PTC 患者 III-IV 期的发生风险较高相关。MDM2 ID 基因型在 40 岁以下的 PTC 患者中显著升高，与更大的肿瘤大小（≥1cm）相关。综上所述，G-D 单倍型而不是 MDM2 309T>G 和 I/D 多态性与 PTC 的发生风险增加相关。MDM2 309T>G 多态性与 III-IV 期发生率较高相关，而 I/D 多态性与肿瘤较大和发病年龄较小相关。
