Laboratory of Cellular and Molecular Tumor Immunology, Department of Hematology, Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Eur J Haematol. 2011 Mar;86(3):199-205. doi: 10.1111/j.1600-0609.2010.01562.x. Epub 2011 Jan 25.
As a component of the MRN complex (which is a heterotrimeric protein complex consisting of MRE11, RAD50 and NBS1), NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. Leukemia is common in NBS1 germ line-mutated patients. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with acute lymphoblastic leukemia (ALL) in Chinese population has not been investigated. Besides, there is no report about the association between NBS1 3'UTR variant rs2735383 and ALL risk. In this study, a multiple centre case-control analysis was performed to assess the association between NBS1 polymorphisms and ALL risk. The genotypes and haplotypes were determined in 175 cases and 350 controls, and the associations with risk of ALL were estimated by logistic regression. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (P(trend) < 0.0001). The allele C increases the risk of ALL in a dose-dependent response manner. These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for developing ALL.
作为 MRN 复合物（由 MRE11、RAD50 和 NBS1 组成的异源三聚体蛋白复合物）的一个组成部分，NBS1 在细胞对 DNA 损伤的反应和维持染色体完整性方面发挥着重要作用。NBS1 种系突变患者中常见白血病。NBS1 E185Q 多态性（8360G>C，rs1805794）在一些癌症中得到了广泛研究，但在中国人群中与急性淋巴细胞白血病（ALL）的关联尚未得到研究。此外，尚无关于 NBS1 3'UTR 变异 rs2735383 与 ALL 风险之间关联的报告。在这项研究中，进行了一项多中心病例对照分析，以评估 NBS1 多态性与 ALL 风险之间的关联。在 175 例病例和 350 例对照中确定了基因型和单倍型，并通过逻辑回归估计了与 ALL 风险的关联。我们观察到病例和对照组之间 rs1805794 C/G 位点的基因型频率存在显著差异（P(trend) < 0.0001）。等位基因 C 以剂量依赖的方式增加 ALL 的风险。这些发现表明，NBS1 中的 E185Q 多态性可能是 ALL 发生的遗传修饰因子。
