Functional analysis and case-control study of -160C/A polymorphism in the E-cadherin gene promoter: association with cancer risk.
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.
Cattaneo
Francesca
F
Department of Genetics and Microbiology, University of Pavia, 27100 Pavia, Italy.
Venesio
Tiziana
T
Molatore
Sara
S
Russo
Antonio
A
Fiocca
Roberto
R
Frattini
Milo
M
Scovassi
A Ivana
AI
Ottini
Laura
L
Bertario
Lucio
L
Ranzani
Guglielmina Nadia
GN
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
D015820:Cadherins; D017931:DNA Primers