Role of HPC2/ELAC2 in hereditary prostate cancer

The HPC2/ELAC2 gene on chromosome 17p was recently identified as a candidate gene for hereditary prostate cancer (HPC). To confirm these findings, we screened 300 prostate cancer patients (2 affected members/family) from 150 families with HPC for potential germ-line mutations using conformation-sens...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-09, Vol.61 (17), p.6494-6499
Main Authors: LIANG WANG, MCDONNELL, Shannon K, BLUTE, Michael L, SCHAID, Daniel J, THIBODEAU, Stephen N, ELKINS, David A, SLAGER, Susan L, CHRISTENSEN, Eric, MARKS, Angela F, CUNNINGHAM, Julie M, PETERSON, Brett J, JACOBSEN, Steven J, CERHAN, James R
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
chromosome 17
Codon, Nonsense
DNA Mutational Analysis
ELAC2 gene
Germ-Line Mutation
HPC2 gene
HPC2/ELAC2 gene
Humans
Male
Medical sciences
Middle Aged
Neoplasm Proteins - genetics
Nephrology. Urinary tract diseases
Pedigree
Polymorphism, Genetic
prostate carcinoma
Prostatic Neoplasms - genetics
Tumors of the urinary system
Urinary tract. Prostate gland
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The HPC2/ELAC2 gene on chromosome 17p was recently identified as a candidate gene for hereditary prostate cancer (HPC). To confirm these findings, we screened 300 prostate cancer patients (2 affected members/family) from 150 families with HPC for potential germ-line mutations using conformation-sensitive gel electrophoresis, followed by direct sequence analysis. The minimum criteria for our families with HPC was the presence of 3 affected men with prostate cancer. A total of 23 variants were identified, including 13 intronic and 10 exonic changes. Of the 10 exonic changes, 1 truncating mutation was identified, a Glu216Stop nonsense mutation. This nonsense variant was found in 2 of 3 affected men in a single family. The remaining nine alterations included five missense, three silent, and one variant in the 3' untranslated region. To additionally test for potential associations of polymorphic variants and increased risk for disease, we genotyped two common polymorphisms, Ser217Leu and Ala541Thr, in 446 prostate cancer patients from 164 families with HPC and 502 population-based controls. The frequency of the Leu217 variant was similar for patients (32.3%) and controls (31.8%), as was the frequency of the Thr541 variant (5.4% among patients versus 5.2% among controls). In contrast to previous reports, we found no association of the joint effects of Leu271 and Thr541 (odds ratio, 1.04; 95% confidence interval, 0.57-1.89). Overall, our results did not reveal any association between these two common polymorphisms and the risk for HPC. The finding of a nonsense mutation in the HPC2/ELAC2 gene confirms its potential role in genetic susceptibility to prostate cancer. However, our data also suggest that germ-line mutations of the HPC2/ELAC2 are rare in HPC and that the variants Leu217 and Thr541 do not appear to influence the risk for HPC. Cumulatively, these results suggest that alterations within the HPC2/ELAC2 gene play a limited role in genetic susceptibility to HPC.
ISSN:0008-5472
1538-7445