Department of Gastroenterology, Jiangsu Taizhou People's Hospital, Taizhou, PR China.
Department of Paediatrics, Jiangsu Taizhou People's Hospital, Taizhou, PR China.
Clin Res Hepatol Gastroenterol. 2019 Jun;43(3):324-329. doi: 10.1016/j.clinre.2018.10.013. Epub 2018 Nov 15.
Recent meta-analysis of genome-wide association studies (GWASs) identified a novel variant rs992157 at 2q35 that was associated with colorectal cancer (CRC) in the population of European ancestry. We aimed to replicate the association of rs992157 with CRC in the Chinese population and to further determine the real susceptible gene of CRC as indicated by this variant.
824 CRC patients and 1063 healthy controls were included. The frequency of the genotype and the allele of rs992157 were compared between the patients and the controls and between different subgroups of patients classified by status of metastasis. Expression level of TMBIM1 was compared between the tumor tissue and the adjacent normal tissues collected from 43 patients during surgery. Besides, the relationship between genotypes of rs992157 and the tissue expression of TMBIM1 was analyzed.
Patients were found to have significantly higher frequency of allele G than the controls (44.2% vs. 40.0%, P = 0.009; OR = 1.18). Moreover, allele G was associated with an increased risk of lymph node metastasis (P = 0.02) and distant metastasis of CRC (P = 0.04). The mean expression level of TMBIM1 was significantly higher in tumor tissue than in the adjacent normal tissues (0.0019 ± 0.00068 vs. 0.00041 ± 0.00024, P < 0.001). In addition, patients with genotype GG were found to have remarkably higher TMBIM1 expression in the tumors than those with genotype AA (0.0024 ± 0.00052 vs. 0.0015 ± 0.00078, P = 0.005).
Variant rs992157 is significantly associated with the susceptibility and progression of CRC. It can increase the risk of CRC possibly via up-regulation of TMBIM1.
最近对全基因组关联研究（GWAS）的荟萃分析确定了一个位于 2q35 的新型变体 rs992157，该变体与欧洲血统人群的结直肠癌（CRC）相关。我们旨在在中国人群中复制 rs992157 与 CRC 的关联，并进一步确定该变体所指示的 CRC 的真正易感基因。
纳入 824 例 CRC 患者和 1063 例健康对照。比较患者与对照之间以及根据转移状态分类的不同患者亚组之间 rs992157 基因型和等位基因的频率。从 43 名手术期间收集的肿瘤组织和相邻正常组织中比较 TMBIM1 的表达水平。此外，还分析了 rs992157 的基因型与 TMBIM1 组织表达之间的关系。
患者的等位基因 G 频率明显高于对照组（44.2% vs. 40.0%，P=0.009；OR=1.18）。此外，等位基因 G 与 CRC 的淋巴结转移（P=0.02）和远处转移风险增加相关（P=0.04）。TMBIM1 的平均表达水平在肿瘤组织中明显高于相邻正常组织（0.0019±0.00068 vs. 0.00041±0.00024，P<0.001）。此外，与基因型 AA 相比，基因型 GG 的患者肿瘤中 TMBIM1 的表达明显更高（0.0024±0.00052 vs. 0.0015±0.00078，P=0.005）。
变体 rs992157 与 CRC 的易感性和进展显著相关。它可能通过上调 TMBIM1 增加 CRC 的风险。
