PCAP is the major known prostate cancer predisposing locus in families from south and west Europe

Abstract

To date four prostate cancer predisposing loci have been mapped: HPC1 (Hereditary Prostate Cancer 1) on 1q24-25, PCaP (Predisposing for Cancer Prostate) on 1q42.2-43, CAPB (Cancer Prostate and Brain) on 1p36, and HPCX on Xq27-28. We examined evidence for linkage to those loci in 64 families from south and west Europe. Genotyping of three (six for PCaP) markers encompassing the candidate regions were performed on 221 individuals including 159 affected patients. The resulting data were analysed using both parametric and non parametric linkage methods. No significant evidence of linkage to HPC1, CAPB, or HPCX was found either in the whole population or when pedigrees were stratified according to criteria specific to each locus. By contrast, results in favour of linkage to PCaP locus were observed with maximum multipoint NPL and HLOD scores of 2.8 (P = 0.0026) and 2.65 respectively. Homogeneity analysis performed with multipoint LOD scores gave an estimated proportion of families with linkage to this locus up to 50%. Particularly, families with an earlier age at diagnosis (465-years-old) contributed significantly to the evidence of linkage with a maximum multipoint NPL score of 2.03 (P = 0.024). Those results suggest that PCaP is the most frequent known locus predisposing to hereditary prostate cancer cases from families from south and west Europe.

A major locus for hereditary prostate cancer in Finland: localization by linkage disequilibrium of a haplotype in the HPCX region

“…Confirmation of linkage to HPCX has been attempted in other studies (Lange et al 1999;Bergthorsson et al 2000;Cancel-Tassin et al 2001;Cussenot and Valeri 2001;Matikaine et al 2001;Peters et al 2001;Bochum et al 2002), and the most significant HPCX confirmation, based on 143 Utah extended high-risk PRCA families, obtained a multipoint TLOD of 2.74 (P=0.0002) (Farnham et al 2004). However, no trait-causing mutations or variants have been reported in this region.…”

Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci

“…Review of the pedigrees from the 33 African American families described in this report reveals no cases of primary brain cancer in first-and/or second-degree relatives. Most of the linkage evidence in support of the PCAP locus at 1q42 -43 is derived from families from France and England (Berthon et al, 1998;Cancel-Tassin et al, 2001); many of the published prostate cancer linkage studies in other populations have not provided significant support for this putative locus (for example, Berry et al, 2000a;Xu et al, 2001). In our study of 32 African American families in which genotype data was available, we did not see significant evidence for linkage.…”

Confirmation of the HPCX prostate cancer predisposition locus in large Utah prostate cancer pedigrees

“…To date, five studies attempting to confirm these findings have been published (Bergthorsson et al 2000;Bochum et al 2002;Cancel-Tassin et al 2001;Lange et al 1999;Peters et al 2001). Of these, only one study attained at least nominal evidence (P<0.05) with Z=2.32 (P=0.009) in a non-parametric linkage analysis of a subset of pedigrees having a younger age-at-diagnosis (Bochum et al 2002).…”