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Functional Polymorphism in the <i>MSI1</i> Gene Promoter Confers a Decreased Risk of Lung Cancer in Chinese by Reducing <i>MSI1</i> Expression

[ Vol. 19 , Issue. 5 ]

Author(s):

Lin Liu, Fuman Qiu, Jiansong Chen, Di Wu, Qingqing Nong, Yifeng Zhou and Jiachun Lu *   Pages 375 - 383 ( 9 )

Abstract:


Background: <i>Musashi1 (MSI1)</i> is a characteristic stem cell marker that regulates the balance between cell self-renewal and differentiation. Evidence has identified <i>MSI1</i> as a pivotal oncogenic regulator in diverse malignancies. However, little evidence uncovers the role of genetic variations of <i>MSI1</i> gene in cancer etiology. </P><P> Objective: The aim of this study was to investigate the association between genetic variants in the <i>MSI1</i> gene and lung cancer risk. </P><P> 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 <i>MSI1</i> promoter (<i>i.e.</i>, -2696T>C[rs7959801], -2297T>C[rs3742038] and -1081C>T[rs34570155]) and lung cancer risk. </P><P> 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 <i>MSI1</i> gene arrestingly decreased its transcription activity in vitro. Furthermore, the expression levels of <i>MSI1</i> were significantly lower in the patients with CT/CC variants than in those who were with TT genotype. </P><P> Conclusion: Our findings suggested that the rs7959801T>C polymorphism in the <i>MSI1</i> promoter conferred a decreased risk to lung cancer by reducing the expression of <i>MSI1</i> and it may be a promising indicator for lung cancer predisposition.

Keywords:

Lung cancer, <i>Musashi1</i>, Promoter, Genetic variant, Susceptibility, Case-control study.

Affiliation:

The State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, The State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, The State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, The State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, Department of Environmental Health, Guangxi Medical University, 22 Shuangyong road, Nanning 530021, Department of Genetics, Medical College of Soochow University, 199 Renai road, Suzhou 215123, The State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120

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