title: Significant association between FasL gene -844T/C polymorphism and risk to hepatocellular carcinoma in Egyptian patients.
abstract: Fas/Fas ligand (FasL) system is the most critical apoptotic signaling entity in the extrinsic apoptotic pathway; hence mutations affecting this pathway may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between the FasL -844T/C polymorphism and the risk of hepatocellular carcinoma (HCC) in a cohort of Egyptian patients and explored the relationship of various clinical and pathological parameters with this single nucleotide polymorphism (SNP). Blood samples were withdrawn from hundred HCC patients and 100 age-, sex- and ethnically matched controls. The FasL -844T/C (rs763110) gene polymorphism was typed from genomic DNA using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Genotype distributions and allelic frequencies between patients and control subjects showed that the TT homozygous patients were two times more likely to develop HCC (p=0.011). Also, the T allele was found to be a significant risk factor for the disease (OR 1.970, 95% CI 1.250-3.105, p=0.003). No association was detected between different parameters of the disease and the SNP. For the first time, our results suggest that the -844T/C polymorphism in the FasL gene confers risk to HCC. The alarming increase in the incidence of HCC in Egypt encourages further studies to document our results in a larger sample, and recommends more genetic studies hoping to define a genomic risk prediction specific to this cancer in our population.
authors.affiliation: Department of Clinical & Chemical Pathology, Kasr Al-Ainy, School of Medicine, Cairo University, Egypt. Electronic address: drrhk@hotmail.com.
authors.forename: Rania H
authors.initials: RH
authors.lastname: Khalifa
authors.affiliation: Department of Clinical & Chemical Pathology, Kasr Al-Ainy, School of Medicine, Cairo University, Egypt.
authors.forename: Dina M Rasheed
authors.initials: DM
authors.lastname: Bahgat
authors.affiliation: Department of Internal Medicine, Kasr Al-Ainy, School of Medicine, Cairo University, Egypt.
authors.forename: Hatem Abdel Hamid
authors.initials: HA
authors.lastname: Darwish
authors.affiliation: Department of Clinical & Chemical Pathology, Kasr Al-Ainy, School of Medicine, Cairo University, Egypt.
authors.forename: Rasha Mohamad Hosny
authors.initials: RM
authors.lastname: Shahin
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004534:Egypt; D053222:Fas Ligand Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein
keywords: Egypt; Fas/Fas ligand; Hepatocellular carcinoma; PCR-RFLP; Polymorphism