Lethal-7-related polymorphisms are associated with susceptibility to and prognosis of gastric cancer
Lethal-7-related polymorphisms are associated with susceptibility to and prognosis of gastric cancer
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Lethal-7相关多态性与胃癌易感性和预后相关
DOI：
10.3748/wjg.v25.i8.1012
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发表时间：
2019-02-28
影响因子：
4.3
通讯作者：
Jiang, Jing
中科院分区：
文献类型：
--
作者：
Jia, Zhi-Fang;Cao, Dong-Hui;Jiang, Jing
背景：lethal-7 （let-7）家族成员及其靶点参与肿瘤的发生和发展。据报道，let -7相关多态性与肿瘤发生和预后有关。然而，在胃癌中，相关研究有限。目的探讨let-7相关microRNA多态性在中国人群胃癌发生及预后中的作用。方法2008 - 2013年共招募898例胃癌患者和992例无肿瘤对照。胃癌患者定期随访。使用MassARRAY系统对let-7基因区域的10个单核苷酸多态性（snp）或其靶mrna进行基因分型，并分析其与胃癌风险或总生存期的相关性。结果10个snp均达到Hardy-Weinberg平衡。在调整年龄和幽门螺杆菌状态后，LIN28A 3 ' -非翻译区（UTR） rs3811463多态性的C等位基因与较低的胃癌风险相关[比值比(OR) = 0.74, 95%可信区间（CI）： 0.61-0.88, P = 0.001]。735例行根治性肿瘤切除术的胃癌患者纳入生存分析，其5年生存率为53.9% （95%CI: 50.1%-57.6%）。il - 23r 3′-UTR中的rs10889677与胃癌预后呈剂量-反应关系，在控制其他潜在临床病理参数后，随着C等位基因数量的增加，死亡风险增加25% [HR = 1.25, 95%CI: 1.04-1.45, P = 0.011]。结论LIN28A中let-7相关多态性rs3811463与胃癌易感性相关，IL23R中let-7相关多态性rs10889677与胃癌预后相关。
BACKGROUND The lethal-7 (let-7) family members and their targets are involved in the development and progression of tumors. Let-7-related polymorphisms have been reported to be associated with tumorigenesis and prognosis. In gastric cancer, however, the related studies are limited. AIM To investigate the role of let-7-related microRNA polymorphisms in the tumorigenesis and prognosis of gastric cancer in a Chinese population. METHODS A total of 898 gastric cancer patients and 992 tumor-free controls were recruited into this study from 2008 to 2013. Gastric cancer patients were followed periodically. Ten single nucleotide polymorphisms (SNPs) in the let-7 gene region or their target mRNAs were genotyped using the MassARRAY system and their associations with the risk for or overall survival of gastric cancer were analyzed. RESULTS All the ten SNPs were in Hardy-Weinberg equilibrium. The C allele of the rs3811463 polymorphism in the 3’-untranslated region (UTR) of LIN28A was associated with a lower risk of gastric cancer [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.61-0.88, P = 0.001] after adjustment for age and Helicobacter pylori status. Seven hundred and thirty-five gastric cancer patients who had undergone radical tumorectomy were included in the survival analysis and their 5-year survival rate was 53.9% (95%CI: 50.1%-57.6%). The rs10889677 in the 3’-UTR of IL23R was corresponded to the prognosis of gastric cancer in a dose-response manner, in which the death risk increased by 25% [hazard ratio (HR) = 1.25, 95%CI: 1.04-1.45, P = 0.011] with each increase in the number of C alleles after controlling for other potential clinicopathological parameters. CONCLUSION The let-7-related polymorphism rs3811463 in LIN28A is associated with the susceptibility to gastric cancer and the let-7-related polymorphism rs10889677 in IL23R is associated with the prognosis of gastric cancer.