The relationship between rs968697 genetic polymorphism and gastric cancer susceptibility, TNM stage and survival prognosis

Jun Hu, Xiaoting Wang
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Abstract

HMGA2 can promote the development of multiple malignancies. This study aimed to determine whether a putative functional genetic polymorphism (rs968697 T>C) in the HMGA2 gene promoter region was associated with malignancy susceptibility in the Chinese population. The rs968697 genetic polymorphism was genotyped using the SNaPshot method in the case-control study. The odds ratios and 95% confidence intervals were calculated using a logistic regression model. STATA software was used to conduct the meta-analysis. The rs968697 genetic polymorphism was associated not only with susceptibility to malignant tumors [CC versus TT: OR = 0.45, 95%CI = 0.28–0.73, p = .001; CC versus (CT + TT): OR = 0.47, 95%CI = 0.29–0.75, p = .003] including gastric cancer (GC), but also with TNM stage and survival prognosis of GC patients. Genotype-tissue expression analysis, luciferase assay and bioinformatics analysis revealed that the rs968697 genetic polymorphism might affect the binding of transcription factors, especially POLR2A, which in turn regulate the expression of HMGA2. The current research suggests that the rs968697 genetic polymorphism may be used as a biomarker for malignancy susceptibility and GC prognosis in the Chinese population.
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rs968697 基因多态性与胃癌易感性、TNM 分期和生存预后的关系
HMGA2 可促进多种恶性肿瘤的发生。本研究旨在确定中国人群中HMGA2基因启动子区的推定功能性基因多态性(rs968697 T>C)是否与恶性肿瘤易感性相关。病例对照研究采用 SNaPshot 方法对 rs968697 基因多态性进行了基因分型。采用逻辑回归模型计算了几率比和 95% 的置信区间。采用 STATA 软件进行荟萃分析。rs968697 基因多态性不仅与恶性肿瘤的易感性相关[CC 与 TT:OR = 0.45,95%CI = 0.28-0.73,p = .001;CC 与(CT + TT):OR = 0.47,95%CI = 0.28-0.73,p = .001;CC 与(CT + TT):OR = 0.47,95%CI = 0.28-0.73,p = .001],而且还与肿瘤的易感性相关:OR = 0.47,95%CI = 0.29-0.75,p = .003],包括胃癌(GC),还与 TNM 分期和胃癌患者的生存预后有关。基因型-组织表达分析、荧光素酶检测和生物信息学分析表明,rs968697 基因多态性可能会影响转录因子(尤其是 POLR2A)的结合,进而调控 HMGA2 的表达。目前的研究表明,rs968697基因多态性可作为中国人群恶性肿瘤易感性和GC预后的生物标志物。
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