title: Impact of insulin-like growth factor 2, insulin-like growth factor receptor 2, insulin receptor substrate 2 genes polymorphisms on susceptibility and clinicopathological features of hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. Insulin-like growth factor-2 (IGF-2) is an important autocrine and paracrine growth factor which may induce cell proliferation and inhibit cell apoptosis leading to the transformation of normal cells into malignant cells. This study aimed to evaluate the possible roles of IGF-2, insulin-like growth factor-2 receptor (IGF-2R), and insulin receptor substrate (IRS)-2 genes polymorphisms in susceptibility and clinicopathological features of HCC in Egyptian population.
  
  
  METHODS
  Four hundred and twenty-six HCC patients and 334 controls were enrolled in the study. Polymorphisms of IGF-2+3580, IGF-2+3123, IGF-2R 1619, and IRS-2 1057 gene were detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IGF-2 were determined using ELISA.
  
  
  RESULTS
  Serum IGF-2 levels were significantly lower in HCC patients than in healthy controls. IGF-2+3580 AA genotype, IGF-2+3123 GG genotype or G allele, IRS-2 1057 DD genotype and D allele were significantly associated with HCC risk. The combination of IGF-2+3580 AA homozygosity and IGF-2R 1619 GG homozygosity presented a significant protective effect against HCC (OR=0.16,95% CI=0. 08-0.34, P=0. 005). Serum IGF-2 concentrations were significantly increased in HCC patients with the IGF-2+3580 AA genotype. We also observed that increased alpha-fetoprotein (AFP), Child-Pugh grade, tumor size, and number of malignant lesions were accompanied by a significant increase of serum IGF-2 mean values of in HCC patients.
  
  
  CONCLUSIONS
  IGF-2, IGF-2R, and IRS-2 genes polymorphisms and their combinations are associated with risk of HCC.
authors.affiliation: Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Nearmeen M
authors.initials: NM
authors.lastname: Rashad
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: amalelshal@yahoo.com.
authors.forename: Amal S
authors.initials: AS
authors.lastname: El-Shal
authors.affiliation: Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Eman H
authors.initials: EH
authors.lastname: Abd Elbary
authors.affiliation: Radiodiagnosis Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Abo Warda
authors.affiliation: Hepatobillary Surgery Department, National Liver Institute, Shebin Elkom, Egypt.
authors.forename: Osama
authors.initials: O
authors.lastname: Hegazy
mesh_terms: D000328:Adult; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D017931:DNA Primers; D004534:Egypt; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D020022:Genetic Predisposition to Disease; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000097:blood / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017527:Receptor, IGF Type 2 / Q000097:blood / Q000235:genetics*
chemical_list: D017931:DNA Primers; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II
keywords: Genes polymorphisms; Hepatocellular carcinoma; Insulin receptor substrate; Insulin-like growth factor-2; Insulin-like growth factor-2 receptor