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Prostate. 2006 Apr 1;66(5):546-56.

E-cadherin polymorphisms and haplotypes influence risk for prostate cancer.

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1
Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus 43210, USA.

Abstract

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.

PMID:
16372334
DOI:
10.1002/pros.20374
[Indexed for MEDLINE]
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