School of Pharmacy, Yancheng Teachers' University, Yancheng, Jiangsu, China.
Physical Examination Centre, Xuhui District Central Hospital of Shanghai, Shanghai, China.
Nucleosides Nucleotides Nucleic Acids. 2021;40(8):821-828. doi: 10.1080/15257770.2021.1952596. Epub 2021 Jul 21.
A genetic polymorphism (rs968697 T > C) in the gene has recently been linked to an increased risk of hepatoblastoma. However, no studies have been conducted to investigate the effect of the polymorphism on the risk of colorectal cancer (CRC). The study aimed to explore whether the rs968697 polymorphism had a significant impact on CRC risk. A total of 500 CRC patients and 500 age and gender matched healthy individuals were genotyped by using the SNaPshot method. Quantitative real-time PCR technology was used to detect the relative expression of the gene in 30 pairs of primary CRC and adjacent non-cancerous tissues. rs968697 polymorphism was significantly associated with CRC risk [CC vs. TT: OR = 0.20, 95%CI = 0.06-0.70, P = 0.01; (CC + CT) vs. TT: OR = 0.71, 95%CI = 0.53-0.96, P = 0.02; CC vs. (CT + TT): OR = 0.21, 95%CI = 0.06-0.73, P = 0.01; C vs. T: OR = 0.67, 95%CI = 0.51-0.89, P < 0.01]. The analysis based on tumor stage indicated that the CRC patients with rs968697 C allele were less likely to have high-stage tumors. Furthermore, the genotype-tissue expression analysis revealed that the rs968697 CC genotype was linked to the low expression of gene. The in silico analysis revealed that the rs968697 polymorphism in the promoter region of the gene could influence transcription factor binding, including ATF6, DBP, CDPCR3, DR3, NRSF, PAX8, PPARA, SZF11, TAXCREB and POLR2A. In conclusion, our findings suggested that the rs968697 polymorphism was linked to CRC risk and could be used as a biomarker to detect CRC risk.
一个基因的遗传多态性（rs968697 T > C）最近与肝母细胞瘤的风险增加有关。然而，目前还没有研究探讨该多态性对结直肠癌（CRC）风险的影响。本研究旨在探讨 rs968697 多态性是否对 CRC 风险有显著影响。采用 SNaPshot 法对 500 例 CRC 患者和 500 例年龄和性别匹配的健康个体进行基因分型。采用实时定量 PCR 技术检测 30 对原发性 CRC 和相邻非癌组织中基因的相对表达。rs968697 多态性与 CRC 风险显著相关[CC 与 TT：OR = 0.20，95%CI = 0.06-0.70，P = 0.01；（CC + CT）与 TT：OR = 0.71，95%CI = 0.53-0.96，P = 0.02；CC 与（CT + TT）：OR = 0.21，95%CI = 0.06-0.73，P = 0.01；C 与 T：OR = 0.67，95%CI = 0.51-0.89，P < 0.01]。基于肿瘤分期的分析表明，携带 rs968697 C 等位基因的 CRC 患者发生高分期肿瘤的可能性较低。此外，基因-组织表达分析显示，rs968697 CC 基因型与基因表达水平较低相关。计算机分析显示，基因启动子区域的 rs968697 多态性可能影响转录因子结合，包括 ATF6、DBP、CDPCR3、DR3、NRSF、PAX8、PPARA、SZF11、TAXC-REB 和 POLR2A。综上所述，本研究结果表明，rs968697 多态性与 CRC 风险相关，可作为检测 CRC 风险的生物标志物。
