Abstract
Hepatocellular carcinoma (HCC) is a major health concern in Egypt owing to the high prevalence of hepatitis C virus (HCV) infection. HCC incidence is characterized by obvious male predominance, yet the molecular mechanisms behind this gender bias are still unidentified. Functional variations in X-linked genes have more impact on males than females. Glypican-3 (GPC3) gene, located in the Xq26 region, has lately emerged as being potentially implicated in hepatocellular carcinogenesis. The current study was designed to examine the association of −784 G/C single nucleotide polymorphism (SNP) in GPC3 promoter region (rs2267531) with HCC susceptibility in male and female Egyptian HCV patients. Our results revealed a significant association between GPC3 and HCC risk in both males and females, evidenced by higher C allele and CC/C genotype frequencies in HCC patients when compared to controls. However, no such association was found when comparing HCV patients to controls. Moreover, GPC3 gene and protein expression levels were significantly higher in CC/C than in GG/G genotype carriers in males and females. The CC/C genotype exhibited a significant shorter overall survival than GG/G genotype in HCC patients. In conclusion, GPC3 rs2267531 on the X chromosome is significantly associated with HCC, but not with HCV infection, in the Egyptian population.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer globally and the third contributor to cancer-related death with about 500000 new cases annually
Our study aimed to explore whether −784 G/C gene polymorphism in the promoter region of GPC3 in males and females is associated with HCC risk in hepatitis C virus (HCV) Egyptian patients
HCV infection, for which Egypt bears the highest incidence in the world, is a major risk factor for the development of HCC
Summary
HCC is the fifth most prevalent cancer globally and the third contributor to cancer-related death with about 500000 new cases annually. The mortality due to HCC is very high, remarkably in patients diagnosed in late-stages due to the lack of symptoms during early stages. This problem is more obvious in developing countries due to poor screening tools[5]. GPC3 is overexpressed in most HCCs but not in cirrhotic liver or in benign hepatic lesions[17,18] It promotes the growth of HCC by increasing c-Myc expression, a usual target of the canonical Wnt signaling pathway[19]. Our study aimed to explore whether −784 G/C gene polymorphism (rs2267531) in the promoter region of GPC3 in males and females is associated with HCC risk in HCV Egyptian patients
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