A single-nucleotide polymorphism in the TP53 and MDM-2 gene modifies breast cancer risk in an ethnic Arab population
A single-nucleotide polymorphism in the TP53 and MDM-2 gene modifies breast cancer risk in an ethnic Arab population
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DOI：
10.1111/j.1472-8206.2011.00939.x
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发表时间：
2012-06-01
影响因子：
2.9
通讯作者：
Alsaif, Adulaziz A.
中科院分区：
文献类型：
--
作者：
Alshatwi, Ali A.;Hasan, Tarique N.;Alsaif, Adulaziz A.
乳腺癌是世界范围内女性最常见的肿瘤疾病。乳腺癌的遗传易感性可能与单核苷酸多态性（SNP）有关，这在许多女性中观察到。这种基因多态性，结合营养和环境因素，可以影响乳腺癌的发展。肿瘤抑制因子TP 53及其负调控因子MDM 2在肿瘤发生中起着重要作用。以往的病例对照研究表明，TP 53 72 Arg> Pro和MDM 2 309 T> G多态性与常见癌症的风险有关。然而，这两个功能多态性和乳腺癌易感性在沙特人口之间的关系尚未探讨。在这项研究中，我们进行了一项病例对照研究，乳腺癌患者和健康对照组在沙特人口使用TaqMan为基础的实时PCR。我们发现MDM 2 GG [比值比（OR）= 2.79，95%可信区间（CI）= 2.043.92]和TG [OR = 1.43，95%CI = 1.122.02]基因型与乳腺癌风险增加相关。与Arg/Arg基因型相比，TP 53 Pro/Pro基因型的患病风险增加（OR = 2.19，95%CI = 1.543.06）。MDM 2和TP 53基因多态性的基因-基因交互作用以倍增方式增加乳腺癌的风险（MDM 2 GG和TP 53 Pro/Pro基因型同时存在的OR = 7.71，95%CI = 3.49 ± 17.54）。这些发现表明，MDM 2和TP 53基因多态性可能是阿拉伯世界这一种族人群中发生乳腺癌的遗传修饰因子。
Breast cancer is the most common oncological disease in women worldwide. Genetic predisposition to breast cancer can be associated with single-nucleotide polymorphisms (SNPs), which are observed in many women. Such gene polymorphisms, in combination with nutritional and environmental factors, can affect breast cancer development. The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous casecontrol studies have revealed that TP53 72Arg > Pro and MDM2 309T > G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and breast cancer susceptibility in the Saudi population has not been explored. In this study, we performed a casecontrol study of patients with breast cancer and healthy controls in a Saudi population using TaqMan-based real-time PCR. We found an increased breast cancer risk associated with the MDM2 GG [odds ratio (OR) = 2.79, 95% confidence interval (CI) = 2.043.92] and TG [OR = 1.43, 95% CI = 1.122.02] genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.19, 95% CI = 1.543.06) compared with the Arg/Arg genotype. The genegene interaction of MDM2 and TP53 polymorphisms increased breast cancer risk in a multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.71, 95% CI = 3.4917.54). These findings suggest that polymorphisms of MDM2 and TP53 genes may be a genetic modifier for developing breast cancer in this ethnic population in the Arab world.