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TP53(R72P)和MDM2(T309G)基因多态性在乳腺癌患者中的临床意义

Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients.

作者信息

Yadav P, Masroor M, Tanwer K, Mir R, Javid J, Ahmad I, Zuberi M, Kaza R C M, Jain S K, Khurana N, Ray P C, Saxena A

机构信息

Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India.

Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, 71491, Saudi Arabia.

出版信息

Clin Transl Oncol. 2016 Jul;18(7):728-34. doi: 10.1007/s12094-015-1425-5. Epub 2015 Nov 9.

Abstract

INTRODUCTION

TP53 gene is the most frequently altered tumor suppressor gene in breast cancer. It has been observed that MDM2 plays a central role in regulating the TP53 pathway. This study aimed to investigate the role of TP53 Arg72Pro and MDM2 T309G polymorphisms in breast cancer patients.

MATERIAL AND METHOD

The TP53 (Arg72Pro) and MDM2 (T309G) polymorphisms were studied in a hospital-based case control study by AS-PCR in 100 breast cancer patients and 100 healthy control subjects.

RESULTS

It was observed that TP53 Arg72Pro polymorphism was significantly associated with breast cancer (χ (2) = 9.92, p = 0.007). A significantly increased breast cancer risk was associated with the Proline allele [odds ratio 1.84 (95 % CI: 1.22-2.77), risk ratio 1.34 (95 % CI: 1.11-1.63), p value 0.003], HER2/neu status (p = 0.01) and distant metastasis (p = 0.05). On the other hand, we have found a significant correlation between MDM2 (T309G) polymorphism with HER2/neu status (χ (2) = 11.14, p = 0.003) and distant metastasis (p value = 0.04).

CONCLUSION

Our finding suggests that TP53 (Arg72Pro) polymorphism may play a significant role as risk factor for breast cancer in north Indian breast cancer patients. While MDM2 (T309G) polymorphism may not be directly associated with the risk of breast cancer occurrence in the same population, but it may play role in disease progression by triggering TP53.

摘要

引言

TP53基因是乳腺癌中最常发生改变的肿瘤抑制基因。据观察,MDM2在调节TP53通路中起核心作用。本研究旨在探讨TP53基因第72位密码子精氨酸突变为脯氨酸(Arg72Pro)和MDM2基因第309位密码子苏氨酸突变为甘氨酸(T309G)多态性在乳腺癌患者中的作用。

材料与方法

在一项基于医院的病例对照研究中,采用等位基因特异性聚合酶链反应(AS-PCR)对100例乳腺癌患者和100例健康对照者的TP53(Arg72Pro)和MDM2(T309G)多态性进行研究。

结果

观察到TP53 Arg72Pro多态性与乳腺癌显著相关(χ² = 9.92,p = 0.007)。脯氨酸等位基因与乳腺癌风险显著增加相关[比值比1.84(95%可信区间:1.22 - 2.77),风险比1.34(95%可信区间:1.11 - 1.63),p值0.003],与HER2/neu状态(p = 0.01)和远处转移(p = 0.05)也相关。另一方面,我们发现MDM2(T309G)多态性与HER2/neu状态(χ² = 11.14,p = 0.003)和远处转移(p值 = 0.04)之间存在显著相关性。

结论

我们的研究结果表明,TP53(Arg72Pro)多态性可能是印度北部乳腺癌患者患乳腺癌的重要危险因素。而MDM2(T309G)多态性可能与同一人群中乳腺癌发生风险无直接关联,但可能通过触发TP53在疾病进展中发挥作用。

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