title: Functional analysis and case-control study of -160C/A polymorphism in the E-cadherin gene promoter: association with cancer risk.
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.
  
  
  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).
  
  
  CONCLUSIONS
  Our data support the notion that the A allele may act as a low-penetrance cancer susceptibility gene.
authors.affiliation: Department of Genetics and Microbiology, University of Pavia, 27100 Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cattaneo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Venesio
authors.forename: Sara
authors.initials: S
authors.lastname: Molatore
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Roberto
authors.initials: R
authors.lastname: Fiocca
authors.forename: Milo
authors.initials: M
authors.lastname: Frattini
authors.forename: A Ivana
authors.initials: AI
authors.lastname: Scovassi
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
authors.forename: Lucio
authors.initials: L
authors.lastname: Bertario
authors.forename: Guglielmina Nadia
authors.initials: GN
authors.lastname: Ranzani
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D015820:Cadherins; D017931:DNA Primers