E-cadherin polymorphisms and haplotypes influence risk for prostate cancer

• Published in: The Prostate 2006-04, Vol.66 (5), p.546-556
• Main Authors: Bonilla, Carolina, Mason, Tshela, Long, Layron, Ahaghotu, Chiledum, Chen, Weidong, Zhao, Aiqiu, Coulibaly, Aoua, Bennett, Frankly, Aiken, William, Tullock, Trevor, Coard, Kathleen, Freeman, Vincent, Kittles, Rick A.
• Format: Article
• Language: English
• Subjects: African Americans; African Americans - genetics; Aged; Biological and medical sciences; Cadherins - genetics; CDH1; Exons; Genetic Predisposition to Disease; Gynecology. Andrology. Obstetrics; haplotypes; Humans; Introns; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Polymorphism, Genetic; Promoter Regions, Genetic; prostate cancer; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - epidemiology; Prostatic Neoplasms - genetics; Risk Factors; Sequence Deletion; single nucleotide polymorphisms (SNP); tumor suppressor; Tumors; Tumors of the urinary system; United States; Urinary tract. Prostate gland
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20374

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. © 2005 Wiley‐Liss, Inc.