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.
Functional analysis and case-control study of -160C/A polymorphism in the E-cadherin gene promoter: association with cancer risk / Cattaneo, F; Venesio, T; Molatore, S; Russo, A; Fiocca, R; Frattini, M; Scovassi, Ai; Ottini, Laura; Bertario, L; Ranzani, Gn. - In: ANTICANCER RESEARCH. - ISSN 0250-7005. - 26(6B):(2006), pp. 4627-4632.
Functional analysis and case-control study of -160C/A polymorphism in the E-cadherin gene promoter: association with cancer risk.
OTTINI, LAURA;
2006
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.