Abstract
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.
Keywords: Lung cancer, Musashi1, Promoter, Genetic variant, Susceptibility, Case-control study.
Current Genomics
Title:Functional Polymorphism in the MSI1 Gene Promoter Confers a Decreased Risk of Lung Cancer in Chinese by Reducing MSI1 Expression
Volume: 19 Issue: 5
Author(s): Lin Liu, Fuman Qiu, Jiansong Chen, Di Wu, Qingqing Nong, Yifeng Zhou and Jiachun Lu *
Affiliation:
- The State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120,China
Keywords: Lung cancer, Musashi1, Promoter, Genetic variant, Susceptibility, Case-control study.
Abstract: 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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Cite this article as:
Liu Lin , Qiu Fuman , Chen Jiansong , Wu Di , Nong Qingqing , Zhou Yifeng and Lu Jiachun *, Functional Polymorphism in the MSI1 Gene Promoter Confers a Decreased Risk of Lung Cancer in Chinese by Reducing MSI1 Expression, Current Genomics 2018; 19 (5) . https://dx.doi.org/10.2174/1389202919666171128151544
DOI https://dx.doi.org/10.2174/1389202919666171128151544 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
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