Functional Polymorphism in the MSI1 Gene Promoter Confers a Decreased Risk of Lung Cancer in Chinese by Reducing MSI1 Expression.
Functional Polymorphism in the MSI1 Gene Promoter Confers a Decreased Risk of Lung Cancer in Chinese by Reducing MSI1 Expression.
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MSI1 基因启动子的功能多态性通过降低 MSI1 表达来降低中国人患肺癌的风险
DOI：
10.2174/1389202919666171128151544
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发表时间：
2018-08
期刊：
影响因子：
2.6
通讯作者：
Lu J
中科院分区：
文献类型：
--
作者：
Liu L;Qiu F;Chen J;Wu D;Nong Q;Zhou Y;Lu J
Musashi 1（MSI 1）是一种特征性的干细胞标志物，调节细胞自我更新和分化之间的平衡。有证据表明MSI 1是多种恶性肿瘤中的关键致癌调节因子。然而，很少有证据揭示MSI 1基因的遗传变异在癌症病因学中的作用。目的：本研究的目的是探讨MSI 1基因的遗传变异与肺癌风险之间的关系。研究方法：基于一项两阶段的回顾性研究，共有1559名肺癌患者和1667名健康对照者，我们评估了MSI 1启动子中三种推定的功能性SNP之间的相关性（即，-2696 T>C[rs7959801]、-2297 T>C[rs3742038]和-1081 C>T[rs34570155]）与肺癌风险的关系。结果：SNP rs7959801 T>C与肺癌易感性显著相关。与rs7959801 TT野生基因型相比，CT/CC变异基因型个体在发现集（校正比值比[OR] = 0.67; 95%置信区间[CI] = 0.57-0.80）和验证集（OR=0.69; 95%CI=0.54-0.88）中对肺癌风险发挥了一致的有益作用。功能分析表明，MSI 1基因rs7959801的T等位基因转化为C等位基因后，其体外转录活性显著降低。CT/CC基因型患者MSI 1的表达水平显著低于TT基因型患者。结论：我们的研究结果表明，MSI 1启动子rs7959801 T>C多态性通过降低MSI 1的表达而降低肺癌的风险，并且它可能是肺癌易感性的一个有希望的指标。
Background: Musashi1 (MSI1) is a characteristic stem cell marker that regulates the balance between cell self-renewal and differentiation. Evidence has identified MSI1 as a pivotal oncogenic regulator in diverse malignancies. However, little evidence uncovers the role of genetic variations of MSI1 gene in cancer etiology. Objective: The aim of this study was to investigate the association between genetic variants in the MSI1 gene and lung cancer risk. Methods: Based on a two-stage retrospective study with a total of 1559 patients with lung cancer and 1667 healthy controls, we evaluated the relevance between three putative functional SNPs in the MSI1 promoter (i.e., -2696T>C[rs7959801], -2297T>C[rs3742038] and -1081C>T[rs34570155]) and lung cancer risk. Results: We found that the SNP rs7959801T>C was significantly associated with lung cancer susceptibility. Compared to those with rs7959801TT wild-genotype, individuals with CT/CC variant genotypes exerted consistently beneficial roles in lung cancer risk in the discovery set (adjusted odd ratios [OR] = 0.67; 95% confidence interval [CI] = 0.57-0.80), and in the validation set (OR=0.69; 95%CI=0.54-0.88). Functional assays indicated that the allele transformation from T to C in rs7959801 of MSI1 gene arrestingly decreased its transcription activity in vitro. Furthermore, the expression levels of MSI1 were significantly lower in the patients with CT/CC variants than in those who were with TT genotype. Conclusion: Our findings suggested that the rs7959801T>C polymorphism in the MSI1 promoter conferred a decreased risk to lung cancer by reducing the expression of MSI1 and it may be a promising indicator for lung cancer predisposition.
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DOI：
10.1126/science.1171837
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rosen JM;Jordan CT
通讯作者：
Jordan CT
影响因子：
5.7
作者：
Keysar SB;Jimeno A
通讯作者：
Jimeno A
CD133 中的 microRNA-135a/b 结合多态性可通过降低 CD133 表达来降低中国人患肺癌的风险和良好的预后
影响因子：
4.7
作者：
Cheng, Mei;Yang, Lei;Lu, Jiachun
通讯作者：
Lu, Jiachun
影响因子：
2.9
作者：
Chen W;Zheng R;Zeng H;Zhang S
通讯作者：
Zhang S
影响因子：
7.5
作者：
Moreira, Andre L.;Gonen, Mithat;Downey, Robert J.
通讯作者：
Downey, Robert J.