Cancer stem cell marker Musashi-1 rs2522137 genotype is associated with an increased risk of lung cancer.
Gene single nucleotide polymorphisms (SNPs) have been extensively studied in association with development and prognosis of various malignancies. However, the potential role of genetic polymorphisms of cancer stem cell (CSC) marker genes with respect to cancer risk has not been examined. We conducted a case-control study involving a total of 1000 subjects (500 lung cancer patients and 500 age-matched cancer-free controls) from northeastern China. Lung cancer risk was analyzed in a logistic regression model in association with genotypes of four lung CSC marker genes (CD133, ALDH1, Musashi-1, and EpCAM). Using univariate analysis, the Musashi-1 rs2522137 GG genotype was found to be associated with a higher incidence of lung cancer compared with the TT genotype. No significant associations were observed for gene variants of CD133, ALDH1, or EpCAM. In multivariate analysis, Musashi-1 rs2522137 was still significantly associated with lung cancer when environmental and lifestyle factors were incorporated in the model, including lower BMI; family history of cancer; prior diagnosis of chronic obstructive pulmonary disease, pneumonia, or pulmonary tuberculosis; occupational exposure to pesticide; occupational exposure to gasoline or diesel fuel; heavier smoking; and exposure to heavy cooking emissions. The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.7686. To our knowledge, this is the first report to show an association between a Musashi-1 genotype and lung cancer risk. Further, the prediction model in this study may be useful in determining individuals with high risk of lung cancer.
Cancer and Stem Cell Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, P.R. China; Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, California, United States of America.
Xu
X
Wang
Cancer and Stem Cell Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, P.R. China; Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, California, United States of America.
Ji-Fan
JF
Hu
Cancer and Stem Cell Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, P.R. China.
Yehui
Y
Tan
Cancer and Stem Cell Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, P.R. China.
Jiuwei
J
Cui
Cancer and Stem Cell Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, P.R. China.
Guanjun
G
Wang
Department of Pharmacy and Pharmacology, University of Bath, Bath, England.
Randall J
RJ
Mrsny
Cancer and Stem Cell Center, First Affiliated Hospital, Jilin University, Changchun, Jilin, P.R. China.
Wei
W
Li
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D012372:ROC Curve; D050697:Retinal Dehydrogenase / Q000235:genetics
D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; D007527:Isoenzymes; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D016601:RNA-Binding Proteins; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase