E-cadherin polymorphisms and haplotypes influence risk for prostate cancer.
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.
Bonilla
Carolina
C
Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus 43210, USA.
Mason
Tshela
T
Long
Layron
L
Ahaghotu
Chiledum
C
Chen
Weidong
W
Zhao
Aiqiu
A
Coulibaly
Aoua
A
Bennett
Frankly
F
Aiken
William
W
Tullock
Trevor
T
Coard
Kathleen
K
Freeman
Vincent
V
Kittles
Rick A
RA
D001741:Black or African American / Q000235:genetics; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D005091:Exons; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion; D014481:United States
D015820:Cadherins; D017430:Prostate-Specific Antigen