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.

MATERIALS AND 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: C Maier, K Rösch, K Herkommer, S Bochum, G Cancel-Tassin, O Cussenot, J Häussler, G Assum, W Vogel, T Paiss
• Journal: European urology (Eur Urol) Vol. 42 Issue 3 Pg. 301-7 (Sep 2002) ISSN: 0302-2838 [Print] Switzerland
• PMID: 12234517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Galectins
• LGALS8 protein, human

Topics

• Galectins (genetics)
• Gene Frequency (genetics)
• Genetic Predisposition to Disease (genetics)
• Genotype
• Germ-Line Mutation (genetics)
• Humans
• Male
• Pedigree
• Prostatic Neoplasms (genetics)
• Risk Factors