BACKGROUND: The E-cadherin (CDH1) gene has been implicated in prostate cancer (PCA) risk, however, the exact mechanism is unknown. Several polymorphisms, such as the C/A variant -160 base pairs from the transcription start site, in the CDH1 gene promoter region have been associated with cancer risk, mainly in European descent populations. METHODS: We screened the entire coding region and 3.0 kilobases of the CDH1 promoter for polymorphisms in 48 African Americans using dHPLC. Twenty-one (21) polymorphisms were observed. Four polymorphisms, including -160C/A, were genotyped in a genetic association study using incident PCA cases (N = 427) and unaffected controls (N = 337) of similar age from three different ethnic groups consisting of African Americans, Jamaicans, and European Americans. RESULTS: We observed a significantly higher frequency of the -160A allele among European American PCA patients (27.5%) compared to the control group (19.7%) (P = 0.04). More importantly, among men of European ancestry under the age of 65 who possess the -160 A allele there was over three times increased risk for prostate cancer (P = 0.05). Also, the AACT haplotype bearing the -160A allele was significantly associated with PCA in European Americans (P = 0.04). CONCLUSIONS: Our data indicate that CDH1 likely is a low-penetrant PCA susceptibility gene, however, population differences in linkage disequilibrium within the CDH1 gene region may influence the effect of susceptibility alleles such as -160A. (c) 2005 Wiley-Liss, Inc.
BACKGROUND: The E-cadherin (CDH1) gene has been implicated in prostate cancer (PCA) risk, however, the exact mechanism is unknown. Several polymorphisms, such as the C/A variant -160 base pairs from the transcription start site, in the CDH1 gene promoter region have been associated with cancer risk, mainly in European descent populations. METHODS: We screened the entire coding region and 3.0 kilobases of the CDH1 promoter for polymorphisms in 48 African Americans using dHPLC. Twenty-one (21) polymorphisms were observed. Four polymorphisms, including -160C/A, were genotyped in a genetic association study using incident PCA cases (N = 427) and unaffected controls (N = 337) of similar age from three different ethnic groups consisting of African Americans, Jamaicans, and European Americans. RESULTS: We observed a significantly higher frequency of the -160A allele among European American PCA patients (27.5%) compared to the control group (19.7%) (P = 0.04). More importantly, among men of European ancestry under the age of 65 who possess the -160 A allele there was over three times increased risk for prostate cancer (P = 0.05). Also, the AACT haplotype bearing the -160A allele was significantly associated with PCA in European Americans (P = 0.04). CONCLUSIONS: Our data indicate that CDH1 likely is a low-penetrant PCA susceptibility gene, however, population differences in linkage disequilibrium within the CDH1 gene region may influence the effect of susceptibility alleles such as -160A. (c) 2005 Wiley-Liss, Inc.
Authors: Sanggu Kim; Namshin Kim; Beihua Dong; David Boren; Serena A Lee; Jaydip Das Gupta; Christina Gaughan; Eric A Klein; Christopher Lee; Robert H Silverman; Samson A Chow Journal: J Virol Date: 2008-08-06 Impact factor: 5.103
Authors: A J M Mol; A A Geldof; G A Meijer; H G van der Poel; R J A van Moorselaar Journal: J Cancer Res Clin Oncol Date: 2007-05-23 Impact factor: 4.553