Abstract

A genetic polymorphism (rs968697 T > C) in the HMGA2 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 HMGA2 gene in 30 pairs of primary CRC and adjacent non-cancerous tissues. Results: HMGA2 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 HMGA2 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 HMGA2 gene. The in silico analysis revealed that the rs968697 polymorphism in the promoter region of the HMGA2 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 HMGA2 rs968697 polymorphism was linked to CRC risk and could be used as a biomarker to detect CRC risk.

摘要

HMGA2基因中的遗传多态性 (rs968697 T > C)最近与肝母细胞瘤的风险增加有关。然而，尚未进行研究来调查多态性对结直肠癌 (CRC) 风险的影响。该研究旨在探讨 rs968697 多态性是否对 CRC 风险有显着影响。使用 SNaPshot 方法对总共 500 名 CRC 患者和 500 名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CRC及邻近非癌组织中HMGA2基因的相对表达量。结果：HMGA2rs968697 多态性与 CRC 风险显着相关 [CC vs. 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 vs. (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，具有HMGA2 rs968697 C 等位基因的 CRC 患者不太可能患有高分期肿瘤。此外，基因型-组织表达分析表明，rs968697 CC 基因型与HMGA2基因的低表达有关。计算机分析显示HMGA2启动子区的 rs968697 多态性基因可以影响转录因子结合，包括 ATF6、DBP、CDPCR3、DR3、NRSF、PAX8、PPARA、SZF11、TAXCREB ​​和 POLR2A。总之，我们的研究结果表明HMGA2 rs968697 多态性与 CRC 风险相关，可用作检测 CRC 风险的生物标志物。