Functional analysis and case-control study of -160C/A polymorphism in the E-cadherin gene promoter: Association with cancer risk

Francesca Cattaneo, Tiziana Venesio, Sara Molatore, Antonio Russo, Roberto Fiocca, Milo Frattini, A. Ivana Scovassi, Laura Ottini, Lucio Bertario, Guglielmina Nadia Ranzani

Research output: Contribution to journalArticle

Abstract

Background: A C→A polymorphism within the CDH1 (E-cadherin) promoter seems to be associated with a reduced efficiency of gene transcription in vitro. Due to the crucial role of E-cadherin in epithelia, tissue-specific effect of C→A change on CDH1 transcription was tested and a case-control study was performed on patients affected with epithelial tumors. Patients and Methods: The -178/+93 CDH1 region containing either C or A nucleotide was inserted upstream of the Luciferase reporter gene in the pGL-2 vector, and the construct activity was assessed by transient transfection assay in HeLa and HCT116 cells. Results: A significantly lower activity for pGL-2A was found compared to pGL-2C, both in HeLa (54% decrease) and in HCT116 (67% decrease) cells. Genotyping of 246 controls and 505 patients affected with breast, gastric, colorectal, cervical and endometrial cancers demonstrated an association between the A allele and an increased risk of colorectal, gastric and endometrial tumors (1.66-, 1.81- and 2.35-fold, respectively). Conclusion: Our data support the notion that the A allele may act as a low-penetrance cancer susceptibility gene.

Original languageEnglish
Pages (from-to)4627-4632
Number of pages6
JournalAnticancer Research
Volume26
Issue number6 B
Publication statusPublished - Nov 2006

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Keywords

  • Cancer risk
  • CDH1 gene
  • Epithelial cells
  • Polymorphism
  • Promoter

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cattaneo, F., Venesio, T., Molatore, S., Russo, A., Fiocca, R., Frattini, M., Scovassi, A. I., Ottini, L., Bertario, L., & Ranzani, G. N. (2006). Functional analysis and case-control study of -160C/A polymorphism in the E-cadherin gene promoter: Association with cancer risk. Anticancer Research, 26(6 B), 4627-4632.