Human Genetics

, Volume 116, Issue 1, pp 43–50

Hereditary prostate cancer in Finland: fine-mapping validates 3p26 as a major predisposition locus

  • Annika Rökman
  • Agnes B. Baffoe-Bonnie
  • Elizabeth Gillanders
  • Henna Fredriksson
  • Ville Autio
  • Tarja Ikonen
  • Kenneth D. GibbsJr
  • MaryPat Jones
  • Derek Gildea
  • Diane Freas-Lutz
  • Carol Markey
  • Mika P. Matikainen
  • Pasi A. Koivisto
  • Teuvo L. J. Tammela
  • Olli P. Kallioniemi
  • Jeffrey Trent
  • Joan E. Bailey-Wilson
  • Johanna Schleutker
Original Investigation

DOI: 10.1007/s00439-004-1214-7

Cite this article as:
Rökman, A., Baffoe-Bonnie, A.B., Gillanders, E. et al. Hum Genet (2005) 116: 43. doi:10.1007/s00439-004-1214-7

Abstract

In a recent genome-wide linkage (GWL) analysis of Finnish families at high risk for prostate cancer, we found two novel putative susceptibility loci at 3p25-p26 and 11q14. Here, we report the fine-mapping of these two critical regions at high resolution with 39 microsatellite markers in 16 families, including multiplex families that were not used in the GWL scan. The maximum multipoint HLOD was 3.39 at 3p26 and 1.42 at 11q14. The highest LOD scores were seen around markers D3S1270 and D3S4559 (α=0.89), covering approximately two megabases. The two known genes in this region CHL1 (cell adhesion molecule with homology to L1CAM) and CNTN6 (contactin 6) were screened for exonic mutations in the families showing the strongest linkage, but no disease-segregating sequence variants were observed. The recombination map pointed to a region proximal to the area of best linkage, suggesting that more genes may need to be investigated as candidates. These results provide strong evidence for the existence of a prostate cancer susceptibility gene at 3p26 in Finnish prostate cancer families. This locus has not been strongly linked with hereditary prostate cancer in other populations. However, the mildly positive 3p LOD scores in a recent GWL analysis of patients from the United States suggest that the locus may also be important in other populations.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Annika Rökman
    • 1
  • Agnes B. Baffoe-Bonnie
    • 2
    • 3
  • Elizabeth Gillanders
    • 3
  • Henna Fredriksson
    • 1
  • Ville Autio
    • 4
  • Tarja Ikonen
    • 1
  • Kenneth D. GibbsJr
    • 3
  • MaryPat Jones
    • 3
  • Derek Gildea
    • 3
  • Diane Freas-Lutz
    • 3
  • Carol Markey
    • 3
  • Mika P. Matikainen
    • 5
  • Pasi A. Koivisto
    • 6
  • Teuvo L. J. Tammela
    • 5
  • Olli P. Kallioniemi
    • 7
  • Jeffrey Trent
    • 8
  • Joan E. Bailey-Wilson
    • 3
  • Johanna Schleutker
    • 1
  1. 1.Laboratory of Cancer Genetics, Institute of Medical TechnologyUniversity of Tampere and Tampere University HospitalTampereFinland
  2. 2.Division of Population ScienceFox Chase Cancer CenterPhiladelphiaUSA
  3. 3.National Human Genome Research InstituteNational Institutes of HealthBethesdaUSA
  4. 4.Research UnitTampere University HospitalTampereFinland
  5. 5.Division of Urology, Tampere University Hospital and Medical SchoolUniversity of TampereTampereFinland
  6. 6.Department of Clinical GeneticsTampere University HospitalTampereFinland
  7. 7.Medical BiotechnologyVTT— Technical Research Centre and University of TurkuTurkuFinland
  8. 8.Translational Genomics Research InstitutePhoenixUSA