School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China.
Department of Clinical Laboratory, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China.
BMC Cancer. 2018 Feb 12;18(1):175. doi: 10.1186/s12885-018-4078-2.
Nijmegen breakage syndrome 1 (NBS1), as a key protein in the DNA double-strand breaks (DSBs) repair pathway, plays an important role in maintaining genomic stability. Although single nucleotide polymorphisms (SNPs) in NBS1 have frequently been studied in multiple cancers, the relationships of two functional NBS1 polymorphisms (rs2735383 and rs1805794) with laryngeal carcinoma are yet unclear. Therefore, in the present study, we performed a case-control study including 342 cases and 345 controls to analyze the associations between two polymorphisms of NBS1 and the risk of laryngeal carcinoma.
We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the genotypes of the functional SNPs in NBS1 gene.
In comparison with the homozygous rs2735383GG genotype, the CC genotype was significantly associated with an increased risk of laryngeal carcinoma (adjusted OR = 1.884, 95%CI = 1.215-2.921). The rs2735383C variant genotypes (GC + CC) conferred a 1.410-fold increased risk of laryngeal carcinoma (adjusted OR = 1.410, 95%CI = 1.004-1.980). Furthermore, when compared to rs2735383GG genotype in laryngeal carcinoma tissues, the combined GC and CC genotypes exerted a significantly lower mRNA level of NBS1 (P = 0.003). In contrast, no significant association was found between rs1805794G > C polymorphism and cancer risk (adjusted OR = 1.074, 95%CI = 0.759-1.518 for GC; adjusted OR = 1.100, 95%CI = 0.678-1.787 for CC; adjusted OR = 1.079, 95%CI = 0.774-1.505 for GC + CC).
These findings indicate that rs2735383G > C polymorphism in NBS1 may play a crucial role in the development of laryngeal carcinoma.
Nijmegen 断裂综合征 1（NBS1）作为 DNA 双链断裂（DSBs）修复途径中的关键蛋白，在维持基因组稳定性方面发挥着重要作用。尽管 NBS1 中的单核苷酸多态性（SNPs）已在多种癌症中得到广泛研究，但两个功能性 NBS1 多态性（rs2735383 和 rs1805794）与喉癌的关系尚不清楚。因此，在本研究中，我们进行了一项病例对照研究，包括 342 例病例和 345 例对照，以分析 NBS1 中两个多态性与喉癌风险之间的关系。
我们使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法确定 NBS1 基因中功能性 SNPs 的基因型。
与 NBS1 基因 rs2735383 的同合子 GG 基因型相比，CC 基因型与喉癌的风险显著增加相关（调整后的 OR=1.884，95%CI=1.215-2.921）。rs2735383 的 C 变体基因型（GC+CC）使喉癌的风险增加 1.410 倍（调整后的 OR=1.410，95%CI=1.004-1.980）。此外，与喉癌组织中的 rs2735383 GG 基因型相比，GC 和 CC 基因型的 NBS1 表达水平显著降低（P=0.003）。相反，rs1805794G>C 多态性与癌症风险之间无显著相关性（GC 的调整后 OR=1.074，95%CI=0.759-1.518；CC 的调整后 OR=1.100，95%CI=0.678-1.787；GC+CC 的调整后 OR=1.079，95%CI=0.774-1.505）。
这些发现表明 NBS1 中的 rs2735383G>C 多态性可能在喉癌的发展中起着关键作用。
