title: A candidate gene approach within the susceptibility region PCaP on 1q42.2-43 excludes deleterious mutations of the PCTA-1 gene to be responsible for hereditary prostate cancer.
abstract: OBJECTIVE
  The Prostate Carcinoma Tumor Antigen-1 (PCTA-1) is located at the prostate cancer susceptibility locus on chromosome 1q42.2-43 (PCaP). In this candidate gene approach, we searched for deleterious mutations within the PCTA-1 gene and its promoter.
  
  
  METHODS
  Seventy-seven familial prostate cancer cases from 36 German and French pedigrees were screened for germline mutations in the PCTA-1 gene using enzymatic mutation detection (EMD). Putative missense mutations were genotyped by RPLP and ddNTP primer extension assays in 88 controls to assess allele frequencies and haplotypes.
  
  
  RESULTS
  Several sequence variants were found but none of the findings indicated a deleterious mutation. Three affected brothers showed an intronic variation, which may interfere with correct splicing. Four non-conservative SNPs were characterized, coding for the amino acid alterations Y19F, C36R, V56M and S184R. All exchanges were found in controls with common allelic frequencies of at least 28%. Haplotype definition including six SNPs within the PCTA-1 gene revealed a complete linkage disequilibrium. Low haplotype diversity leads to a predominance of only two peptide variants of the PCTA-1 protein, coded by 95% of all chromosomes.
  
  
  CONCLUSIONS
  PCTA-1 is not a classical high risk gene with deleterious mutations predisposing to hereditary prostate cancer. Its contribution to prostate cancer susceptibility as a low risk factor in sporadic disease has to be assessed in larger samples by association studies.
authors.affiliation: Abteilung Humangenetik, Universitätsklinikum Ulm, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Maier
authors.forename: K
authors.initials: K
authors.lastname: Rösch
authors.forename: K
authors.initials: K
authors.lastname: Herkommer
authors.forename: S
authors.initials: S
authors.lastname: Bochum
authors.forename: G
authors.initials: G
authors.lastname: Cancel-Tassin
authors.forename: O
authors.initials: O
authors.lastname: Cussenot
authors.forename: J
authors.initials: J
authors.lastname: Häussler
authors.forename: G
authors.initials: G
authors.lastname: Assum
authors.forename: W
authors.initials: W
authors.lastname: Vogel
authors.forename: T
authors.initials: T
authors.lastname: Paiss
mesh_terms: D037161:Galectins / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors
chemical_list: D037161:Galectins; C091991:LGALS8 protein, human