Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies
Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies
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DOI：
10.1002/ijc.21439
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发表时间：
2006-03-01
影响因子：
6.4
通讯作者：
Kowalczyk, J
中科院分区：
文献类型：
--
作者：
Chrzanowska, KH;Piekutowska-Abramczuk, D;Kowalczyk, J
奈亨断裂综合征（NBS）是一种人类常染色体隐性遗传病，其特征是基因组不稳定和癌症易感性增加，特别是淋巴瘤和白血病。最近，在散发性淋巴恶性肿瘤的俄罗斯儿童和非霍奇金淋巴瘤（NHL）的波兰成人中，发现斯拉夫创始人NBS1突变657del5的杂合携带者的频率明显较高。此外，在急性淋巴细胞白血病（ALL）患儿中，也发现643C >t （R215W）取代物过量。为了评估这两种突变对散发性淋巴细胞恶性肿瘤发展的贡献，我们分析了来自一大群波兰儿科患者的DNA样本。270例ALL患者中有3例，212例儿童和青少年NHL患者中有2例存在一个等位基因上的NBS1突变657de15；63例霍奇金淋巴瘤（HL）患者中未发现携带者。在所有研究组中均未检测到变异R215W的携带者。657del5突变的相对频率是根据患者居住地匹配的6,984例对照计算得出的，其中42例为携带者（频率= 0.006）。在分析的恶性肿瘤人群中，与对照波兰人群相比，突变657de15发生的优势比增加（OR范围1.48-1.85,95%置信区间1.18-2.65）。这一发现表明突变携带者的频率确实在ALL和NHL患者中增加（p < 0.05）。然而，NBS1基因杂合性并不是儿童和青少年淋巴细胞恶性肿瘤的主要危险因素。(c) 2005 Wiley-Giss, Inc。
Nijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non-Hodgkin lymphoma (NHL). In addition, the substitution 643C > T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657de15 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency = 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657de15 was found in comparison with the control Polish population (OR range 1.48-1.85, 95% confidence interval 1.18-2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence. (c) 2005 Wiley-Giss, Inc.