TP53基因多态性变异在慢性淋巴细胞白血病中的临床相关性

Clinical relevance of TP53 polymorphic genetic variations in chronic lymphocytic leukemia.

作者信息

Bilous Nadiia, Abramenko Iryna, Saenko Vladimir, Chumak Anatoliy, Dyagil Iryna, Martina Zoya, Kryachok Iryna

机构信息

Department of Clinical Immunology, Research Center for Radiation Medicine, 119/121 Prospect Peremohy Str., 03115, Kyiv, Ukraine.

Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.

出版信息

Leuk Res. 2017 Jul;58:1-8. doi: 10.1016/j.leukres.2017.03.009. Epub 2017 Mar 16.

DOI:10.1016/j.leukres.2017.03.009

PMID:28364582

Abstract

OBJECTIVES

To analyze the distribution of single nucleotide polymorphisms (SNPs) in the TP53 gene in chronic lymphocytic leukemia (CLL) patients and to evaluate their associations with clinical behavior of the disease.

METHODS

SNPs in exons and parts of adjacent introns of the TP53 gene were analyzed in 235 CLL patients observed during 2005-2012 years. Data on individuals of European descent from the 1000 Genomes Project data set were used as a reference.

RESULTS

In the recessive model of inheritance, we found borderline associations between CLL risk and C/C genotype of rs1642785 (p=0.048); G/G genotype of rs2909430 (in men only; p=0.036) and Pro72Pro genotype of rs1042522 (in men only; p=0.045). Risk of CLL was increased also in carriers of rare haplotypes (p=0.0049). Besides, genotypes Pro72Pro of rs1042522, C/C of rs1642785, and G/G of rs2909430 were associated with an increased incidence of TP53 mutations. Median of overall survival in rs1800372 carriers was comparable to that of patients with TP53 mutations. Other evaluated SNPs were not associated with survival.

CONCLUSION

Our data suggest that some TP53 variants may affect the risk of CLL. rs1800372 polymorphism might be the marker of unfavorable prognosis of the disease.

摘要

目的

分析慢性淋巴细胞白血病（CLL）患者TP53基因单核苷酸多态性（SNP）的分布，并评估其与疾病临床行为的相关性。

方法

对2005年至2012年期间观察的235例CLL患者的TP53基因外显子及部分相邻内含子中的SNP进行分析。以1000基因组计划数据集中欧洲血统个体的数据作为参考。

结果

在隐性遗传模型中，我们发现rs1642785的C/C基因型与CLL风险之间存在临界相关性（p=0.048）；rs2909430的G/G基因型（仅在男性中；p=0.036）以及rs1042522的Pro72Pro基因型（仅在男性中；p=0.045）。罕见单倍型携带者的CLL风险也增加（p=0.0049）。此外，rs1042522的Pro72Pro基因型、rs1642785的C/C基因型以及rs2909430的G/G基因型与TP53突变发生率增加相关。rs1800372携带者的总生存中位数与TP53突变患者相当。其他评估的SNP与生存无关。