Carcinogenesis Advance Access published online on July 1, 2004
Carcinogenesis, doi:10.1093/carcin/bgh223
© 2004 by Oxford University Press
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1 Korean Hereditary Tumor Registry, Laboratory of Cell Biology, Cancer Research Institute and Cancer Research Center, Seoul National University, Korea
* To whom correspondence should be addressed. E-mail: park{at}ncc.re.kr.
E-cadherin, the main adhesion molecule of epithelial cells, has been implicated in carcinogenesis because its expression is frequently lost in human epithelial cancers. E-cadherin protein expression is significantly reduced in sporadic colorectal cancers, but apparently not as a consequence of allele loss or somatic mutation. We recently reported that a single nucleotide polymorphism (-347 G
Revised June 18, 2004
Accepted June 22, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
A functional polymorphism (-347 G
GA) in the E-cadherin gene is associated with colorectal cancer
2 Department of Surgery, Seoul National University Hospital, Seoul, Korea
3 Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea
4 Korean Hereditary Tumor Registry, Laboratory of Cell Biology, Cancer Research Institute and Cancer Research Center, Seoul National University, Korea; Department of Surgery, Seoul National University Hospital, Seoul, Korea; Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea
Abstract 
GA) in the E-cadherin promoter suppressed E-cadherin expression and was associated with familial gastric cancer. Here we sought to investigate whether the functional polymorphisms of E-cadherin might affect colorectal cancer. We genotyped 407 individuals (260 colorectal cancer patients and 147 normal controls) for the -347 GGA promoter polymorphism of E-cadherin using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. We also measured the activity of promoters harboring the polymorphism by dual luciferase reporter assay in several colorectal cancer cell lines. We found that the E-cadherin GA genotype (G/GA heterozygous and GA homozygous) was more common in colorectal cancer patients than in normal controls (p = 0.011). Subjects with the E-cadherin GA genotype had an overall 1.75-fold increased risk of colorectal cancer. We also observed an increased risk association between the E-cadherin GA genotype and both proximal colon (p = 0.019) and distal colorectal cancer (p = 0.036). Interestingly, the GA allele decreased transcriptional efficiency by 12-, 9- and, 10-fold compared with the G allele in SNU-C4, SNU-C5, and SNU-1033 cell lines, respectively. Additionally, we examined whether there was correlation between the E-cadherin promoter polymorphism and microsatellite instability (MSI) status, and found no such correlation. Taken together, our results suggest that the E-cadherin -347 GGA polymorphism may be associated with colorectal cancer.
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