title: Genetic polymorphisms in the Wnt/β-catenin pathway genes as predictors of tumor development and survival in patients with hepatitis B virus-associated hepatocellular carcinoma.
abstract: OBJECTIVE
  Wnt/β-catenin signaling has a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). The present study aimed to determine whether genetic variation in the Wnt/β-catenin signaling pathway is associated with the development and/or progression of HCC and the survival of patients with hepatitis B virus (HBV)-associated HCC.
  
  
  METHODS
  We assessed seven single nucleotide polymorphisms (SNPs) of the AXIN1, AXIN2, CTNNB1, and WNT2 genes in 245 patients with HBV-associated HCC and 483 chronic HBV carriers without HCC. We analyzed the association of each SNP with HCC development or progression and overall survival.
  
  
  RESULTS
  The CTNNB1 rs3864004 A allele was associated with a decreased risk of HCC development (P=0.049). Haplotype analysis revealed a significantly higher frequency of CTNNB1 G-A/G-A haplotype at rs3864004 and rs4135385 positions in patients with HCC than in chronic HBV carriers without HCC (P=0.042). The AXIN1 rs1805105 T>C SNP was associated with small tumor size and early tumor stage and the WNT2 rs39315 G allele was associated with advanced tumor stage in HCC. In Kaplan-Meier analysis, carriers of the AXIN1 rs214252 C allele showed longer survival than those with the TT genotype (P=0.020). In multivariate Cox regression analysis, absence of CTNNB1 haplotype A-A at rs3864004 and rs4135385 positions and advanced tumor stage were independent poor predictors of patient survival in patients with HCC.
  
  
  CONCLUSIONS
  These findings suggest that the genetic polymorphisms in CTNNB1 gene might affect tumor development and survival in patients with HBV-associated HCC.
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Soon Sun
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Clinical Trial Center, Ajou University Hospital, Suwon, South Korea.
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Choong Kyun
authors.initials: CK
authors.lastname: Noh
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Kee Myung
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Byung Moo
authors.initials: BM
authors.lastname: Yoo
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea. Electronic address: jaeyoun620@gmail.com.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
mesh_terms: D000328:Adult; D000483:Alleles; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000235:genetics / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D051153:Wnt Proteins / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin
keywords: CTNNB1 AXIN1; Hepatitis B virus; Hepatocellular carcinoma; Single nucleotide polymorphism