Liver Intestine-Cadherin (CDH17) Haplotype Is Associated with Increased Risk of Hepatocellular Carcinoma
Purpose: 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 nu...
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| Published in | Clinical cancer research Vol. 12; no. 17; pp. 5248 - 5252 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Philadelphia, PA
American Association for Cancer Research
01.09.2006
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Purpose: 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.
Experimental Design: 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 χ 2 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.
Conclusion: 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. |
|---|---|
| AbstractList | Abstract
Purpose: 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.
Experimental Design: 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 χ2 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.
Conclusion: 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. PURPOSEHepatocellular 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.EXPERIMENTAL DESIGNWe 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.RESULTSGenotypes 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.CONCLUSIONThe 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. Purpose: 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. Experimental Design: 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 χ 2 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. Conclusion: 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. 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. 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. 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. 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. PURPOSE: 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. Experimental Design: 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 chi super(2) 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. CONCLUSION: 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. |
| Author | Ronnie T.P. Poon George K. Lau Karen S. Liu Pauline P. Leung David W. Ho Sheung Tat Fan Man Ting So Siu Tim Cheung Cindy K. Cheung Qi Cai Chee Kin Hui Xiaoping Miao John Wong Mercè Garcia-Barcelo Brian Y. Lam Silvana S. Lau Ashley S. Wong John M. Luk Xiao Qi Wang Wan Ching Yu |
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| Cites_doi | 10.1038/ng0802-339 10.1073/pnas.91.5.1858 10.1111/j.1749-6632.2000.tb05236.x 10.1016/j.bbrc.2004.04.197 10.1093/hmg/2.6.803 10.1111/j.1349-7006.2003.tb01459.x 10.1002/jcu.1870210502 10.1136/gut.49.1.73 10.1016/S0140-6736(03)14964-1 10.1158/1078-0432.483.11.2 10.1086/319501 10.1016/j.bbrc.2003.10.032 10.1053/j.gastro.2004.09.014 10.1007/978-1-4757-3656-4 10.1006/scbi.2000.0319 10.1093/bioinformatics/17.8.738 10.1002/path.1741 10.1007/s100380200086 |
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| Keywords | Liver cancer Digestive system Risk factor Gut Digestive diseases Hepatic disease Hepatocellular carcinoma Malignant tumor Cadherin Epidemiology Haplotype |
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| Snippet | Purpose: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously
showed that aberrant... Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant mRNA... Abstract Purpose: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that... PURPOSE: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant... PURPOSEHepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant... |
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| SubjectTerms | Alleles Antineoplastic agents Biological and medical sciences Cadherins - genetics Carcinoma, Hepatocellular - diagnosis Carcinoma, Hepatocellular - epidemiology Carcinoma, Hepatocellular - genetics Case-Control Studies China - epidemiology Female Gastroenterology. Liver. Pancreas. Abdomen Genetic Predisposition to Disease Haplotypes haploytpe Hepatocellular carcinoma Humans liver intestine-cadherin Liver Neoplasms - diagnosis Liver Neoplasms - epidemiology Liver Neoplasms - genetics Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Middle Aged Pharmacology. Drug treatments Polymorphism, Single Nucleotide - genetics polymorphisms Risk Factors Tumors |
| Title | Liver Intestine-Cadherin (CDH17) Haplotype Is Associated with Increased Risk of Hepatocellular Carcinoma |
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