Chrzanowska Krystyna H, Piekutowska-Abramczuk Dorota, Popowska Ewa, Gładkowska-Dura Małgorzata, Małdyk Jadwiga, Syczewska Małgorzata, Krajewska-Walasek Małgorzata, Goryluk-Kozakiewicz Bozenna, Bubała Halina, Gadomski Artur, Gaworczyk Anna, Kazanowska Bernarda, Kołtan Andrzej, Kuźmicz Marta, Luszawska-Kutrzeba Teresa, Maciejka-Kapuścińska Lucyna, Stolarska Małgorzata, Stefańska Katarzyna, Sznurkowska Katarzyna, Wakulińska Anna, Wieczorek Maria, Szczepański Tomasz, Kowalczyk Jerzy
Department of Medical Genetics, Children's Memorial Health Institute, 04-730 Warsaw, Al. Dzieci Polskich 20, Poland.
Int J Cancer. 2006 Mar 1;118(5):1269-74. doi: 10.1002/ijc.21439.
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 657del5 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 657del5 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.
奈梅亨断裂综合征（NBS）是一种常染色体隐性遗传病，其特征为基因组不稳定和癌症易感性增加，尤其是淋巴瘤和白血病。最近，在患有散发性淋巴恶性肿瘤的俄罗斯儿童以及患有非霍奇金淋巴瘤（NHL）的波兰成年人中，发现斯拉夫始祖NBS1突变657del5的杂合携带者频率显著更高。此外，在急性淋巴细胞白血病（ALL）患儿中也发现643C>T（R215W）替代突变出现频率过高。为了评估这两种突变对散发性淋巴恶性肿瘤发生的影响，我们分析了一大组波兰儿科患者的DNA样本。在270例ALL患者中有3例、212例儿童和青少年NHL患者中有2例在一个等位基因上发现了NBS1突变657del5；在63例霍奇金淋巴瘤（HL）患者中未发现携带者。在任何研究组中均未检测到R215W变体的携带者。根据总共6984名与患者居住地匹配的对照计算出657del5突变的相对频率，其中42名被发现为携带者（频率=0.006）。在分析的恶性肿瘤人群中，与波兰对照人群相比，发现657del5突变发生的优势比增加（优势比范围为1.48 - 1.85，95%置信区间为1.18 - 2.65）。这一发现表明，ALL和NHL患者中突变携带者的频率确实增加了（p<0.05）。尽管如此，NBS1基因杂合性并非儿童和青少年淋巴恶性肿瘤的主要危险因素。
