Analysis of Xq27-28 Linkage in the International Consortium for Prostate Cancer Genetics (ICPCG) Families Public Deposited

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  • Badzioch, Michael D
    • Other Affiliation: ACTANE consortiumDivision of Medical Genetics, University of Washington Medical Center, Seattle, WA, USA
  • Wiklund, Fredrik
    • Other Affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • Deutsch, Kerry
    • Other Affiliation: FHCRC ICPCG Group, Seattle, WA, USA; Institute for Systems Biology, Seattle, WA, USA
  • Foulkes, William D
    • Other Affiliation: ACTANE consortium; Program in Cancer Genetics, McGill University, Montreal, QC, Canada
  • Hoegel, Josef
    • Other Affiliation: University of Ulm ICPCG Group, Ulm, Germany; Institute of Human Genetics, University of Ulm, Ulm, Germany
  • Isaacs, Sarah D
    • Other Affiliation: Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
  • Lange, Ethan
    • Affiliation: School of Medicine, Department of Genetics
    • Other Affiliation: University of Michigan ICPCG Group, Ann Arbor, MI, USA
  • Wiley, Kathleen E
    • Other Affiliation: Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
  • English, Dallas R
    • Other Affiliation: ACTANE consortium; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
  • Farnham, James M
    • Other Affiliation: University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA
  • Bochum, Sylvia
    • Other Affiliation: University of Ulm ICPCG Group, Ulm, GermanyInstitute of Human Genetics, University of Ulm, Ulm, Germany
  • Cussenot, Olivier
    • Other Affiliation: CeRePP ICPCG Group, 75020, Paris, France; Hopital Tenon, Assistance Publique-Hopitaux de Paris, 75020, Paris, France
  • Powell, Isaac
    • Other Affiliation: African American Hereditary Prostate Cancer ICPCG Group, Phoenix, AZ, USA; Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
  • George, Asha
    • Other Affiliation: Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, 21224, USA; African American Hereditary Prostate Cancer ICPCG Group, Phoenix, AZ, USA; Fox Chase Cancer Center, Philadelphia, PA, USA
  • Emanuelsson, Monica
    • Other Affiliation: Oncologic Centre, Umeå University, Umeå, Sweden
  • Ostrander, Elaine A
    • Other Affiliation: FHCRC ICPCG Group, Seattle, WA, USA; Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
  • Hopper, John L
    • Other Affiliation: ACTANE consortium; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
  • Dimitrov, Latchezar
    • Other Affiliation: Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
  • Edwards, Steve
    • Other Affiliation: ACTANE consortium; Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK
  • Hsieh, Chih-Lin
    • Other Affiliation: BC/CA/HI ICPCG Group, Stanford, CA, USA; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Ageles, CA, USA
  • McIntosh, Laura
    • Other Affiliation: FHCRC ICPCG Group, Seattle, WA, USA; Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA, USA
  • Isaacs, William B
    • Other Affiliation: Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
  • Thibodeau, Stephen N
    • Other Affiliation: Mayo Clinic, Rochester, MN, USA
  • Cannon-Albright, Lisa A
    • Other Affiliation: University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USAGeorge E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA
  • Severi, Gianluca
    • Other Affiliation: ACTANE consortium; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
  • Hebbring, Scott
    • Other Affiliation: Mayo Clinic, Rochester, MN, USA
  • Walsh, Patrick C
    • Other Affiliation: Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
  • Cropp, Cheryl D
    • Other Affiliation: Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, 21224, USA
  • Møller, Pål
    • Other Affiliation: ACTANE consortium; Department of Medical Genetics, Oslo University Hospital, The Norwegian Radium Hospital, Oslo,Norway
  • Oakley-Girvan, Ingrid
    • Other Affiliation: BC/CA/HI ICPCG Group, Stanford, CA, USA; Department of Health Research and Policy; Stanford Cancer Institute, Stanford School of Medicine, Stanford, CA, USA; Cancer Prevention Institute of California
  • Valeri, Antoine
    • Other Affiliation: CeRePP ICPCG Group, 75020, Paris, France
  • Whittemore, Alice S
    • Other Affiliation: BC/CA/HI ICPCG Group, Stanford, CA, USA; Department of Health Research and Policy; Stanford Cancer Institute, Stanford School of Medicine, Stanford, CA, USA
  • Carpten, John D
    • Other Affiliation: African American Hereditary Prostate Cancer ICPCG Group, Phoenix, AZ, USA; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, AZ, USA
  • Childs, Erica J
    • Other Affiliation: Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, 21224, USA; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  • Eeles, Rosalind
    • Other Affiliation: ACTANE consortiumInstitute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK
  • McDonnell, Shannon K
    • Other Affiliation: Mayo Clinic, Rochester, MN, USA
  • Tammela, Teuvo LJ
    • Other Affiliation: University of Tampere ICPCG Group, Tampere, Finland; Institute of Biomedical Technology, University of Tampere, Tampere, Finland; Centre for Laboratory Medicine and Department of Urology, Tampere University Hospital, Tampere, Finland
  • Guy, Michelle
    • Other Affiliation: ACTANE consortiumInstitute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK
  • Xu, Jianfeng
    • Other Affiliation: Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
  • Mæhle, Lovise
    • Other Affiliation: ACTANE consortium; Department of Medical Genetics, Oslo University Hospital, The Norwegian Radium Hospital, Oslo,Norway
  • Giles, Graham G
    • Other Affiliation: ACTANE consortium; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
  • Maier, Christiane
    • Other Affiliation: University of Ulm ICPCG Group, Ulm, Germany; Dept of Urology, University of Ulm, Ulm, Germany; Institute of Human Genetics, University of Ulm, Ulm, Germany
  • Easton, Douglas
    • Other Affiliation: ACTANE consortium; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK
  • Schaid, Daniel J
    • Other Affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA
  • Cancel-Tassin, Geraldine
    • Other Affiliation: CeRePP ICPCG Group, 75020, Paris, France
  • Grönberg, Henrik
    • Other Affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • Bailey-Wilson, Joan E
    • Other Affiliation: Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, 21224, USA; African American Hereditary Prostate Cancer ICPCG Group, Phoenix, AZ, USA; University of Tampere ICPCG Group, Tampere, Finland
  • Karyadi, Danielle M
    • Other Affiliation: FHCRC ICPCG Group, Seattle, WA, USA; Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
  • Cooney, Kathleen A
    • Other Affiliation: University of Michigan ICPCG Group, Ann Arbor, MI, USA; University of Michigan, Ann Arbor, MI, USA
  • Camp, Nicola J
    • Other Affiliation: University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, USA
  • Schleutker, Johanna
    • Other Affiliation: University of Tampere ICPCG Group, Tampere, Finland; Institute of Biomedical Technology, University of Tampere, Tampere, Finland; Centre for Laboratory Medicine and Department of Urology, Tampere University Hospital, Tampere, Finland
  • Stanford, Janet L
    • Other Affiliation: FHCRC ICPCG Group, Seattle, WA, USA; Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA, USA
Abstract
  • Abstract: Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
Date of publication
Identifier
  • 22712434
  • doi:10.1186/1471-2350-13-46
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Joan E Bailey-Wilson et al.; licensee BioMed Central Ltd.
License
Journal title
  • BMC Medical Genetics
Journal volume
  • 13
Journal issue
  • 1
Page start
  • 46
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2350
Bibliographic citation
  • BMC Medical Genetics. 2012 Jun 19;13(1):46
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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