rs401681 and rs402710 confer lung cancer susceptibility by regulating TERT expression instead of CLPTM1L in East Asian populations.
Carcinogenesis
; 39(10): 1216-1221, 2018 10 08.
Article
em En
| MEDLINE
| ID: mdl-29939218
ABSTRACT
Lung cancer is a common cancer in human and has presented significant genetic predisposition. Previous genome-wide association study observed that rs401681 within CLPTM1L (CLPTM1 like) was significantly associated with lung cancer. By analyzing 1000 genomes data for East Asian, we identified only one SNP in nearby region, rs402710, in high linkage disequilibrium with rs401681, which was also associated with lung cancer. However, the real causal SNP and mechanism for the association were still not clear. The following plasmid construction, mutagenesis, transient transfection and luciferase reading indicated that both SNPs could regulate gene expression in lung/bronchial epithelium Beas-2B cell line. By chromosome conformation capture, it was identified that the segment containing these two SNPs could interact with TERT (telomerase reverse transcriptase) promoter, thus indicating that these SNPs confer lung cancer risk by regulating TERT expression instead of CLPTM1L. Through chromatin immunoprecipitation, the transcript factors HNF4A (hepatocyte nuclear factor 4 alpha) and MAF1 (MAF1 homolog, negative regulator of RNA polymerase III) were recognized for the regions spanning rs401681 and rs402710, respectively. Our results uncovered a complete link between these two SNPs and lung cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Telomerase
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Povo Asiático
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Neoplasias Pulmonares
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Proteínas de Membrana
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article