mA 调节因子中的遗传变异与胃癌风险相关。
Genetic variants in mA regulators are associated with gastric cancer risk.
机构信息
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
出版信息
Arch Toxicol. 2021 Mar;95(3):1081-1088. doi: 10.1007/s00204-020-02958-1. Epub 2021 Jan 4.
N-methyladenosine (mA) modification plays a vital regulatory role in tumorigenesis and development. In this study, we determined that the mRNA expression of IGF2BP1, IGF2BP2 and IGF2BP3, as the mA modification genes, was significantly increased in gastric cancer (GC) tissues. Using a logistic regression model, we found that novel single-nucleotide polymorphism (SNP) rs9906944 C > T in IGF2BP1 was remarkably associated with a decreased risk of GC in discovery stage (odds ratio (OR) = 0.75, 95% confidence interval (95% CI): 0.60-0.93, P = 8.51 × 10). This finding was repeated in an independent Nanjing population (OR = 0.76, 95% CI: 0.59-0.98, P = 3.45 × 10). The combined analysis including 2900 GC cases and 3,536 controls confirmed the association between rs9906944 C > T and GC risk (OR = 0.75, 95% CI: 0.64-0.88, P = 5.76 × 10). Furthermore, we found that GC patients with higher IGF2BP1 mRNA expression level had prominent poorer overall survival (hazard ratio (HR) = 1.49, 95% CI: 1.16-1.91, logrank P = 1.50 × 10). For the first time, our findings suggested the importance of genetic variants in mA regulators in GC and indicated that IGF2BP1 plays a crucial role in GC. Genetic variants in mA modification genes may be used for GC risk prediction.
N6-甲基腺苷(mA)修饰在肿瘤发生和发展中发挥着重要的调控作用。在这项研究中,我们确定 IGF2BP1、IGF2BP2 和 IGF2BP3 的 mRNA 表达作为 mA 修饰基因,在胃癌(GC)组织中显著增加。使用逻辑回归模型,我们发现 IGF2BP1 中的新型单核苷酸多态性(SNP)rs9906944C>T 与 GC 的发病风险显著降低有关(优势比(OR)=0.75,95%置信区间(95%CI):0.60-0.93,P=8.51×10-3)。这一发现在南京独立人群中得到了重复(OR=0.76,95%CI:0.59-0.98,P=3.45×10-3)。包括 2900 例 GC 病例和 3536 例对照的联合分析证实了 rs9906944C>T 与 GC 风险之间的关联(OR=0.75,95%CI:0.64-0.88,P=5.76×10-3)。此外,我们发现 IGF2BP1 mRNA 表达水平较高的 GC 患者总体生存明显较差(风险比(HR)=1.49,95%CI:1.16-1.91,logrank P=1.50×10-3)。这是首次发现 mA 调节因子中的遗传变异在 GC 中的重要性,并表明 IGF2BP1 在 GC 中发挥关键作用。mA 修饰基因中的遗传变异可能用于 GC 风险预测。