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细胞周期蛋白 D1 G870A 多态性:与 ALL 发病风险、预后影响和甲氨蝶呤细胞毒性的关系。

Cyclin D1 G870A Polymorphism: Relation to the Risk of ALL Development, Prognosis Impact, and Methotrexate Cytotoxicity.

机构信息

Hematology Unit, Department of Clinical Pathology, Mansoura University, Egypt.

Department of Pediatric, Mansoura University, Egypt.

出版信息

Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2941-2947. doi: 10.31557/APJCP.2020.21.10.2941.

Abstract

BACKGROUND

Cyclin D1 (CCND1) regulates cell cycle progression during the late G1 and S phase and takes part in methotrexate metabolism. It was hypothesized that CCND1 gene polymorphism affects acute lymphoblastic leukemia (ALL) development, prognosis and may relate to methotrexate cytotoxicity.

SUBJECTS AND METHODS

This study included 50 ALL patients and 50 healthy controls, CCND1 G870A polymorphism was studied in all items using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and evaluated methotrexate cytotoxicity for ALL patients using liver function tests before and after methotrexate treatment. We followed up patients for one year to determine disease-free survival (DFS) and overall survival (OS) and its relation to the CCND1 genotype.

RESULTS

We found that AA genotype and A allele have a higher risk of developing ALL compared to the control group. Additionally, we found no notable association between CCND1 variant and methotrexate cytotoxicity and no role of CCND1 polymorphism in ALL prognosis.

CONCLUSION

Our results suggested that CCND1 G870A polymorphism is associated with a high risk of ALL development. However, it has no role in ALL prognosis or methotrexate cytotoxicity.

摘要

背景

细胞周期蛋白 D1(CCND1)在 G1 晚期和 S 期调节细胞周期进程,并参与甲氨蝶呤代谢。有人假设 CCND1 基因多态性影响急性淋巴细胞白血病(ALL)的发展、预后,并且可能与甲氨蝶呤的细胞毒性有关。

对象和方法

本研究纳入了 50 例 ALL 患者和 50 例健康对照者,使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对所有患者研究 CCND1 G870A 多态性,并在甲氨蝶呤治疗前后通过肝功能检查评估 ALL 患者的甲氨蝶呤细胞毒性。我们对患者进行了为期一年的随访,以确定无病生存(DFS)和总生存(OS)及其与 CCND1 基因型的关系。

结果

我们发现与对照组相比,AA 基因型和 A 等位基因发生 ALL 的风险更高。此外,我们未发现 CCND1 变异与甲氨蝶呤细胞毒性之间存在显著关联,也未发现 CCND1 多态性在 ALL 预后中的作用。

结论

我们的结果表明 CCND1 G870A 多态性与 ALL 发病风险增加有关。然而,它在 ALL 预后或甲氨蝶呤细胞毒性中不起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa6d/7798150/3085d32d25b0/APJCP-21-2941-g001.jpg

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