A genetic variant in the promoter of CD46 is associated with the risk and prognosis of hepatocellular carcinoma.
Mol Carcinog
; 59(11): 1243-1255, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-32869896
ABSTRACT
CD46 (also known as membrane cofactor protein), which is a member of the membrane-bound complement regulatory protein family, has been reported to cause cancer cells to escape complement-dependent cytotoxicity. However, the association between CD46 polymorphisms and the risk of hepatocellular carcinoma (HCC) has not been investigated. This two-stage association study was conducted to assess the relationship between the tagging single nucleotide polymorphisms (tagSNPs) of CD46 and HCC risk and prognosis. A series of functional analyses were performed to study the underlying mechanisms. Among the eight tagSNPs, rs2796267 (P = .003) and rs2796268 (P = .011) were found to modify HCC risk in the discovery set. Only rs2796267 (P < .0001) was confirmed to be associated with HCC susceptibility in the validation set. Compared with the wild-type AA genotype, the GG genotype significantly increased the HCC risk (adjusted odds ratio [OR] = 2.03; 95% confidence interval [CI], 1.34-3.08; P = .001). Moreover, subgroups analysis suggested a positive correlation among male and younger patients, especially among drinkers, smokers, and hepatitis B surface antigen-positive individuals. In functional analyses, we found that the rs2796267 G allele in the promoter region of CD46 could increase the expression of CD46 by affecting the binding affinity of STAT5a. Furthermore, Cox regression analysis revealed that the rs2796267 AG/GG genotype was significantly associated with worse prognosis of resected patients with HCC (hazard ratio = 2.27; 95% CI, 1.27-4.05; P = .006). These results suggest that the CD46 rs2796267 polymorphism may contribute to susceptibility and prognosis of HCC by altering promoter activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
/
Regulación Neoplásica de la Expresión Génica
/
Regiones Promotoras Genéticas
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Carcinoma Hepatocelular
/
Polimorfismo de Nucleótido Simple
/
Proteína Cofactora de Membrana
/
Neoplasias Hepáticas
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
China