Mutation screen and association study of EZH2 as a susceptibility gene for aggressive prostate cancer.
BACKGROUND
Several linkage studies have provided evidence for a prostate cancer aggressiveness gene on chromosome 7q. This report details the results of the first mutation screen and association study of EZH2 (located at 7q35) as a potential candidate gene for the development of aggressive prostate cancer.


METHODS
In 10 families with linkage of chromosome 7q31-33 to aggressive prostate cancer, we sequenced the promoter region and all 20 exons of EZH2. We genotyped 11 variants in 287 prostate cancer probands and 96 controls. Association between the disease and the variants/haplotypes was evaluated taking into account clinical data and disease recurrence.


RESULTS
The individual variation sites did not show significant differences in the allele frequencies between cases and controls. In contrast, one haplotype had a higher frequency in controls, and another haplotype was significantly more frequent in cases with low grade tumors (GI/II) and progression free survival (NED).


CONCLUSIONS
We have possibly identified haplotypes which mark alleles that have a beneficial effect on the development of prostate cancer. Moreover, our results suggest that genetic variations of the EZH2 gene are not responsible for the linkage of 7q to aggressive prostate cancer.
Bachmann
Natascha
N
Department of Human Genetics, University of Ulm, Ulm, Germany.
Hoegel
Josef
J
Haeusler
Juergen
J
Kuefer
Rainer
R
Herkommer
Kathleen
K
Paiss
Thomas
T
Vogel
Walther
W
Maier
Christiane
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2