title: Relationship of insulin-like growth factors system gene polymorphisms with the susceptibility and pathological development of hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. The insulin-like growth factors (IGFs) system consists of a group of proteins which may induce cell proliferation and inhibit cell apoptosis through several signal pathways, leading to transformation of normal cells into cancer cells. However, the impact of genetic polymorphisms of the IGFs system on HCC has not been clarified.
  
  
  METHODS
  In this case-control study, a total of 102 HCC patients and 306 age- and gender-matched controls were recruited. The genetic polymorphisms of the IGFs system genes, including IGF-1, IGF-2, IGF-1receptor (IGF-1R), IGF-2R, IGF binding protein (IGFBP-3), and insulin (INS) genes, were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and real-time PCR genotyping analysis.
  
  
  RESULTS
  A significant difference (p = 0.02) between case and control group in the distribution frequency of IGF-2 +3580 polymorphism was observed. Multiple regression model analysis showed that the presence of AA or AG at IGF-2R may exhibit a potential protective effect against hepatitis C [odds ratio (OR) = 0.35, 95% confidence interval (CI) = 0.15-0.82]. The combination of IGF-2 +3580 AA genotype and IGF-2R GG genotype may present a significantly lower risk of HCC (OR = 0.20, 95% CI = 0.05-0.87). Additionally, no polymorphisms of any IGFs system genes were associated with liver-related clinicopathological markers in serum.
  
  
  CONCLUSIONS
  Among IGFs system genes, IGF-2 and IGF-2R gene polymorphisms and combination could be considered as the most important factors contributing to increased susceptibility and pathological development of HCC.
authors.affiliation: Tainan University of Technology, Tainan, Taiwan.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Weng
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Chiung-Man
authors.initials: CM
authors.lastname: Tsai
authors.forename: Yin-Hung
authors.initials: YH
authors.lastname: Chu
authors.forename: Kwo-Chang
authors.initials: KC
authors.lastname: Ueng
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Yeh
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Su
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chen
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D017526:Receptor, IGF Type 1 / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics; D012307:Risk Factors; D013002:Somatomedins / Q000235:genetics*
chemical_list: C515497:IGFBP3 protein, human; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D017527:Receptor, IGF Type 2; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1