title: Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was triggered by the specific constellation of two CDH17 single nucleotide polymorphisms (651T and IVS6+35G). CDH17 aberrant splicing was highly associated with tumor dissemination and shorter survival of HCC patients. Consequently, it is highly relevant to assess whether the presence of these single nucleotide polymorphisms in the general population represents a risk to the development of HCC.
  
  
  METHODS
  We conducted a case-control study including 164 HCC and 99 cirrhosis patients and 293 healthy controls. Genotyping was done by PCR and direct sequencing. Odds ratio (OR) and chi2 analysis were used to analyze genotypes and haplotypes.
  
  
  RESULTS
  Genotypes 651TT [OR, 2.62; 95% confidence interval (95% CI), 1.34-5.03] and IVS6+35 GG (OR, 1.95; 95% CI, 1.04-3.62) were highly associated with HCC disease. The 651T (C>T) and IVS6+35G (A>G) alleles were also overrepresented in HCC patients and, in particular, the T-G haplotype was the most prevalent in HCC patients when compared with healthy controls (OR, 1.57; 95% CI, 1.167-2.109; P=0.004), which was in agreement with the aberrant splicing observed in tumor tissues. There was no significant difference in genotype and allele frequencies between cirrhosis patients and controls.
  
  
  CONCLUSIONS
  The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a genetic susceptibility factor for the development of HCC in a Chinese population.
authors.affiliation: Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Xiao Qi
authors.initials: XQ
authors.lastname: Wang
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
authors.forename: Mercè
authors.initials: M
authors.lastname: Garcia-Barcelo
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Pauline P
authors.initials: PP
authors.lastname: Leung
authors.forename: David W
authors.initials: DW
authors.lastname: Ho
authors.forename: Siu Tim
authors.initials: ST
authors.lastname: Cheung
authors.forename: Brian Y
authors.initials: BY
authors.lastname: Lam
authors.forename: Cindy K
authors.initials: CK
authors.lastname: Cheung
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Wong
authors.forename: Silvana S
authors.initials: SS
authors.lastname: Lau
authors.forename: Man Ting
authors.initials: MT
authors.lastname: So
authors.forename: Wan Ching
authors.initials: WC
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Cai
authors.forename: Karen S
authors.initials: KS
authors.lastname: Liu
authors.forename: Chee Kin
authors.initials: CK
authors.lastname: Hui
authors.forename: George K
authors.initials: GK
authors.lastname: Lau
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
mesh_terms: D000483:Alleles; D015820:Cadherins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: C490584:CDH17 protein, human; D015820:Cadherins