Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China.
Mol Carcinog. 2011 Sep;50(9):689-96. doi: 10.1002/mc.20803. Epub 2011 Jun 7.
As a component of the MRN (MRE11/RAD50/NBS1) complex, NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with nasopharyngeal carcinoma (NPC) in Chinese population has not been investigated. Moreover, there is no report about the association between NBS1 3'UTR variant rs2735383 and the risk of NPC. A multiple center case-control analysis was performed to assess the association between NBS1 polymorphisms and NPC risk in Eastern and Southern Chinese population. The genotypes and haplotypes were determined in 1052 cases and 1168 controls and the associations with risk of NPC were estimated by logistic regression. Cell migration assays were performed in 24-well transwell chambers to detect the effects of NBS1 E185Q SNP on cell migration. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (P(trend) < 0.0001). The C allele increases the risk for invasive disease or metastatic disease, compared with G allele. More over, CNE-2 cells (NPC cell line) transfected with pcDNA-NBS1-185Q (8360CC) had significantly higher migration levels than those transfected with pcDNA-NBS1-185E (8360GG) (P = 0.024). These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for the occurrence and aggression of NPC.
作为 MRN（MRE11/RAD50/NBS1 复合物）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 E185Q 多态性（8360G>C，rs1805794）在一些癌症中经常被研究，但结果不一致，但其与中国人群鼻咽癌（NPC）的关联尚未被研究。此外，尚无关于 NBS1 3'UTR 变体 rs2735383 与 NPC 风险之间的关联的报告。进行了一项多中心病例对照分析，以评估 NBS1 多态性与中国东南人群 NPC 风险的关联。在 1052 例病例和 1168 例对照中确定了基因型和单倍型，并通过 logistic 回归估计了它们与 NPC 风险的关联。在 24 孔 Transwell 室中进行细胞迁移测定，以检测 NBS1 E185Q SNP 对细胞迁移的影响。我们观察到病例组和对照组在 rs1805794 C/G 位点的基因型频率存在显著差异（P(trend) < 0.0001）。与 G 等位基因相比，C 等位基因增加了侵袭性疾病或转移性疾病的风险。此外，转染 pcDNA-NBS1-185Q（8360CC）的 CNE-2 细胞（NPC 细胞系）的迁移水平明显高于转染 pcDNA-NBS1-185E（8360GG）的细胞（P = 0.024）。这些发现表明，NBS1 中的 E185Q 多态性可能是 NPC 发生和侵袭的遗传修饰因子。
