Mutation screening and association study of the candidate prostate cancer susceptibility genes MSR1, PTEN, and KLF6

Prostate. 2006 Jul 1;66(10):1052-60. doi: 10.1002/pros.20425.

Abstract

Background: MSR1, PTEN, and KLF6 have been implicated as candidate susceptibility genes for prostate tumorigenesis.

Methods: Three hundred Jewish prostate cancer patients were screened for alterations in these genes.

Results: MSR1 was conserved in all patients. PTEN screening revealed a novel missense mutation and a silent change. Five KLF6 alterations were detected in 17 patients, including Q160X, the only nonsense KLF6 germline mutation described to date in a cancer patient. The KLF6 IVS1-27G>A polymorphism, recently associated with prostate cancer risk, was detected in 11.9% of the patients and 17.3% of the controls (P = 0.043). IVS1-27A allele frequency was significantly lower in prostate cancer patients (P = 0.030), specifically in Ashkenazi patients (P = 0.047) compared to controls.

Conclusions: We found no evidence that MSR1 and PTEN germline mutations are associated with prostate cancer risk in Jews. The negative association between KLF6 IVS1-27A and prostate cancer risk supports a population-specific effect of susceptibility alleles in prostate tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genetic Testing*
  • Genotype
  • Germ-Line Mutation
  • Humans
  • Israel
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / physiology
  • Male
  • Middle Aged
  • Mutation, Missense
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / physiology
  • Pedigree
  • Polymorphism, Genetic
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / physiopathology
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Scavenger Receptors, Class A / genetics*
  • Scavenger Receptors, Class A / physiology

Substances

  • DNA, Neoplasm
  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors
  • MSR1 protein, human
  • Proto-Oncogene Proteins
  • Scavenger Receptors, Class A
  • PTEN Phosphohydrolase
  • PTEN protein, human