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 (⩽65-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.
Similar content being viewed by others
Article PDF
References
Steinberg GD, Carter BS, Beaty TH, Childs B, Walsh PC: . Family history and the risk of prostate cancer. Prostate 1990 17: 337–347.
Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC: . Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci USA 1992 89: 3367–3371.
Carter BS, Bova GS, Beaty TH et al:. Hereditary prostate cancer: epidemiologic and clinical features. J Urol 1993 150: 797–802.
Gronberg H, Damber L, Damber JE, Iselius L: . Segregation analysis of prostate cancer in Sweden: support for dominant inheritance. Am J Epidemiol 1997 146: 552–557.
Schaid DJ, McDonnell SK, Blute ML, Thibodeau SN: . Evidence for autosomal dominant inheritance of prostate cancer. Am J Hum Genet 1998 62: 1425–1438.
Smith JR, Freije D, Carpten JD et al:. Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search. Science 1996 274: 1371–1374.
Gronberg H, Xu J, Smith JR et al:. Early age at diagnosis in families providing evidence of linkage to the hereditary prostate cancer locus (HPC1) on chromosome 1. Cancer Res 1997 57: 4707–4709.
McIndoe RA, Stanford JL, Gibbs M et al:. Linkage analysis of 49 high-risk families does not support a common familial prostate cancer-susceptibility gene at 1q24-25. Am J Hum Genet 1997 61: 347–353.
Eeles RA, Durocher F, Edwards S et al:. Linkage analysis of chromosome 1q markers in 136 prostate cancer families. Am J Hum Genet 1998 62: 653–658.
Berthon P, Valeri A, Cohen-Akenine A et al:. Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2-43. Am J Hum Genet 1998 62: 1416–1424.
Goode EL, Stanford JL, Chakrabarti L et al:. Linkage analysis of 150 high-risk prostate cancer families at 1q24-25. Genet Epidemiol 2000 18: 251–275.
Cooney KA, McCarthy JD, Lange E et al:. Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study. J Natl Cancer Inst 1997 89: 955–959.
Hsieh CL, Oakley-Girvan I, Gallagher RP et al:. Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study. J Natl Cancer Inst 1997 89: 1893–1894.
Neuhausen SL, Farnham JM, Kort E, Tavtigian SV, Skolnick MH, Cannon-Albright LA: . Prostate cancer susceptibility locus HPC1 in Utah high-risk pedigrees. Hum Mol Genet 1999 8: 2437–2442.
Xu J and the International Consortium for Prostate Cancer Genetics: . Combined analysis of hereditary prostate cancer linkage to 1q24-25: results from 772 hereditary prostate cancer families from the international consortium for prostate cancer genetics. Am J Hum Genet 2000 66: 945–957.
Whittemore AS, Lin IG, Oakley-Girvan I et al:. No evidence of linkage for chromosome 1q42.2-43 in prostate Cancer. Am J Hum Genet 1999 65: 254–256.
Gibbs M, Chakrabarti L, Stanford JL et al:. Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer. Am J Hum Genet 1999 64: 1087–1095.
Berry R, Schaid DJ, Smith JR et al:. Linkage analyses at the chromosome 1 loci 1q24-25 (HPC1), 1q42.2-43 (PCAP), and 1p36 (CAPB) in families with hereditary prostate cancer. Am J Hum Genet 2000 66: 539–546.
Xu J, Meyers D, Freije D et al:. Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat Genet 1998 20: 175–179.
Lange EM, Chen H, Brierley K et al:. Linkage analysis of 153 prostate cancer families over a 30-cM region containing the putative susceptibility locus HPCX. Clin Cancer Res 1999 5: 4013–4020.
Gibbs M, Stanford JL, McIndoe RA et al:. Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. Am J Hum Genet 1999 64: 776–787.
Lathrop GM, Lalouel JM, Julier C, Ott J: . Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 1984 81: 3443–3446.
Cottingham Jr RW, Idury RM, Schaffer AA: . Faster sequential genetic linkage computations. Am J Hum Genet 1993 53: 252–263.
Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES: . Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet 1996 58: 1347–1363.
Ott J: . Analysis of Human Genetic Linkage (revised edition). Johns Hopkins University Press, Baltimore 1991
Gronberg H, Smith J, Emanuelsson M et al:. In Swedish families with hereditary prostate cancer, linkage to the HPC1 locus on chromosome 1q24-25 is restricted to families with early-onset prostate cancer. Am J Hum Genet 1999 65: 134–140.
Acknowledgements
We would like to thank Emmanuelle Guillaume, Marc Guérard, Patrice Morant and Isabelle Gauthier for technical assistance. We acknowledge Dr David J Grausz for critical reading of the manuscript. We would like to thank the families for their participation and the French Association of Urology (AFU) for its continuous support of this programme. We are grateful to the clinicians who referred the families. This work was supported by grants from Association pour la Recherche sur le Cancer (ARC 5441), INSERM (4R004C) and ARITT (IdF 99).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cancel-Tassin, G., Latil, A., Valéri, A. et al. PCAP is the major known prostate cancer predisposing locus in families from south and west Europe. Eur J Hum Genet 9, 135–142 (2001). https://doi.org/10.1038/sj.ejhg.5200592
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ejhg.5200592