Laboratory of Study and Applications of DNA Polymorphisms, Department of Pathological Science, Biological Science Center, State University of Londrina, Campus Universitário-Rod. Celso Garcia Cid (PR 445) Km 380, Londrina, PR, CEP 86051-970, Brazil.
Mol Biol Rep. 2013 Jul;40(7):4591-6. doi: 10.1007/s11033-013-2551-1. Epub 2013 May 8.
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Genetic polymorphisms in the 3'UTR region of the CXCL12 (rs1801157) and TP53 codon 72 (rs1042522) genes may contribute to susceptibility to childhood ALL because they affect some important processes, such as metastasis regulation and tumor suppression. Thus the objective of the present study was to detect the frequency of two genetic polymorphisms in ALL patients and controls and to add information their impact on genetic susceptibility and prognosis. The CXCL12 and TP53 polymorphisms were tested in 54 ALL child patients and in 58 controls by restriction fragment length polymerase chain reaction and allelic specific chain reaction techniques, respectively. The frequencies of both allelic variants were higher in ALL patients than in the controls and indicated a positive association: OR = 2.44; 95 % CI 1.05-5.64 for CXCL12 and OR = 2.20; 95 % CI 1.03-4.70 for TP53. Furthermore, when the two genetic variants were analyzed together, they increased significantly more than fivefold the risk of this neoplasia development (OR = 5.24; 95 % CI 1.39-19.75), indicating their potential as susceptibility markers for ALL disease and the relevance of the allelic variant combination to increased risk of developing malignant tumors. Future studies may indicate a larger panel of genes involved in susceptibility of childhood ALL and other hematological neoplasias.
急性淋巴细胞白血病(ALL)是最常见的儿科恶性肿瘤。CXCL12(rs1801157)和 TP53 密码子 72(rs1042522)基因 3'UTR 区域的遗传多态性可能导致儿童 ALL 的易感性,因为它们影响一些重要的过程,如转移调节和肿瘤抑制。因此,本研究的目的是检测 ALL 患者和对照中两种遗传多态性的频率,并提供有关其对遗传易感性和预后影响的信息。通过限制性片段长度聚合酶链反应和等位基因特异性链反应技术,分别在 54 名 ALL 患儿患者和 58 名对照中检测了 CXCL12 和 TP53 多态性。两种等位基因变体的频率在 ALL 患者中均高于对照组,表明存在正相关:CXCL12 的比值比(OR)为 2.44;95%可信区间(CI)为 1.05-5.64,TP53 的 OR 为 2.20;95%CI 为 1.03-4.70。此外,当同时分析两种遗传变异时,它们使这种肿瘤发展的风险增加了五倍以上(OR=5.24;95%CI 为 1.39-19.75),表明它们可能是 ALL 疾病的易感性标志物,以及等位基因变体组合与恶性肿瘤风险增加的相关性。未来的研究可能会表明涉及儿童 ALL 和其他血液系统肿瘤易感性的更大基因面板。