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
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.