Mutation screen and association study of EZH2 as a susceptibility gene for aggressive prostate cancer

Prostate. 2005 Nov 1;65(3):252-9. doi: 10.1002/pros.20296.

Abstract

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).

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • DNA, Neoplasm / genetics*
  • DNA-Binding Proteins
  • Enhancer of Zeste Homolog 2 Protein
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Polycomb Repressive Complex 2
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Proteins / genetics*
  • Sequence Analysis, DNA
  • Transcription Factors

Substances

  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Proteins
  • Transcription Factors
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2