Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma.
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.
Wang
Xiao Qi
XQ
Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong.
Luk
John M
JM
Garcia-Barcelo
Mercè
M
Miao
Xiaoping
X
Leung
Pauline P
PP
Ho
David W
DW
Cheung
Siu Tim
ST
Lam
Brian Y
BY
Cheung
Cindy K
CK
Wong
Ashley S
AS
Lau
Silvana S
SS
So
Man Ting
MT
Yu
Wan Ching
WC
Cai
Qi
Q
Liu
Karen S
KS
Hui
Chee Kin
CK
Lau
George K
GK
Poon
Ronnie T P
RT
Wong
John
J
Fan
Sheung Tat
ST
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
C490584:CDH17 protein, human; D015820:Cadherins