Journal Article

A functional polymorphism (−347 G→GA) in the <i>E-cadherin</i> gene is associated with colorectal cancer

Yong Shin, Il-Jin Kim, Hio Chung Kang, Jae-Hyun Park, Hye-Won Park, Sang-Geun Jang, Min Ro Lee, Seung-Yong Jeong, Hee Jin Chang, Ja-Lok Ku and Jae-Gahb Park

in Carcinogenesis

Volume 25, issue 11, pages 2173-2176
Published in print November 2004 | ISSN: 0143-3334
Published online November 2004 | e-ISSN: 1460-2180 | DOI:
A functional polymorphism (−347 G→GA) in the E-cadherin gene is associated with colorectal cancer

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  • Clinical Cytogenetics and Molecular Genetics


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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 (CRC), but apparently not as a consequence of allele loss or somatic mutation. We reported recently that a single nucleotide polymorphism (−347 G→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 CRC. We genotyped 407 individuals (260 CRC patients and 147 normal controls) for the −347 G→GA promoter polymorphism of E-cadherin using denaturing high-performance liquid chromatography and direct sequencing. We also measured the activity of promoters harboring the polymorphism by dual luciferase reporter assay in several CRC cell lines. We found that the E-cadherin GA genotype (G/GA heterozygous and GA homozygous) was more common in CRC patients than in normal controls (P = 0.011). Subjects with the E-cadherin GA genotype had an overall 1.75-fold increased risk of CRC. We also observed an increased risk association between the E-cadherin GA genotype and both proximal colon (P = 0.019) and distal CRC (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 a correlation between the E-cadherin promoter polymorphism and microsatellite instability status, and found no such correlation. Taken together, our results suggest that the E-cadherin −347 G→GA polymorphism may be associated with CRC.

Keywords: CRC, colorectal cancer; MSI, microsatellite instability; MSS, microsatellite stability

Journal Article.  2843 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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