Nature Genetics
20, 175 - 179 (1998)
doi:10.1038/2477
Evidence for a prostate cancer susceptibility locus on the X chromosome.
Jianfeng Xu *1, Deborah Meyers1, Diha Freije2, Sarah Isaacs2, Kathy Wiley2, Deborah Nusskern2, Charles Ewing2, Eric Wilkens2, Piroska Bujnovszky2, G. Steven Bova2, 3, Patrick Walsh2, William Isaacs2, 4, Johanna Schleutker *5, Mika Matikainen *5, Teuvo Tammela5, Tapio Visakorpi5, Olli-P. Kallioniemi12, Rebecca Berry *6, Daniel Schaid *7, Amy French6, Shannon McDonnell7, Jennifer Schroeder6, Michael Blute8, Stephen Thibodeau6, Henrik Grönberg *9, Monika Emanuelsson9, Jan-Erik Damber10, Anders Bergh11, Björn-Anders Jonsson11, Jeffrey Smith *12, Joan Bailey-Wilson12, John Carpten12, Dietrich Stephan12, Elizabeth Gillanders12, Isaac Amundson12, Tommi Kainu12, Diana Freas-Lutz12, Agnes Baffoe-Bonnie13, Anne Van Aucken12, Raman Sood12, Francis Collins12, Michael Brownstein12
& Jeffrey Trent121
Center for the Genetics of Asthma and Complex Diseases,
University of Maryland, Baltimore, Maryland
21201, USA. 2
Department of Urology, Johns Hopkins Medical Institutions
, Baltimore, Maryland 21287, USA
. 3
Department of Pathology, Johns Hopkins Medical Institutions
, Baltimore, Maryland 21287, USA
. 4
Department of Oncology, Johns Hopkins Medical Institutions
, Baltimore, Maryland 21287, USA
. 5
Laboratory of Cancer Genetics, Institute of Medical
Technology, University of Tampere and Tampere University Hospital,
Tampere, Finland. 6
Department of Laboratory Medicine and Pathology, Mayo
Clinic/Foundation, Rochester, Minnesota 55902
, USA. 7
Department of Health Sciences Research, Mayo Clinic/Foundation
, Rochester, Minnesota 55902, USA
. 8
Department of Urology, Mayo Clinic/Foundation,
Rochester, Minnesota 55902, USA. 9
Department of Oncology, Umeå University,
Umeå, Sweden. 10
Department of Urology & Andrology, Umeå
University, Umeå, Sweden. 11
Department of Pathology, Umeå University,
Umeå, Sweden. 12
Prostate Cancer Investigation Group, National Human
Genome Research Institute, National Institute of Health, Bethesda
, Maryland 20892, USA. 13
Population Science Division, Fox Chase Cancer Center
, Philadelphia, Pennsylvania 19012,
USA. *These authors contributed equally to this work.
Correspondence should be addressed to wisaacs@jhmi.eduOver 200,000 new prostate cancer cases are diagnosed in the United States
each year, accounting for more than 35% of all cancer cases affecting men,
and resulting in 40,000 deaths annually1. Attempts to characterize
genes predisposing to prostate cancer have been hampered by a high phenocopy
rate, the late age of onset of the disease and, in the absence of distinguishing
clinical features, the inability to stratify patients into subgroups relative
to suspected genetic locus heterogeneity. We previously performed a genome-wide
search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate
cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a
second prostate cancer susceptibility gene, which by heterogeneity estimates
accounts for approximately 16% of HPC cases. This HPC locus resides on the
X chromosome (Xq27-28), a finding consistent with results of previous population-based
studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28
was observed in a combined study population of 360 prostate cancer families
collected at four independent sites in North America, Finland and Sweden.
A maximum two-point lod score of 4.60 was observed at DXS1113,  =0.26,
in the combined data set. Parametric multipoint and non-parametric analyses
provided results consistent with the two-point analysis. evidence for genetic
locus heterogeneity was observed, with similar estimates of the proportion
of linked families in each separate family collection. Genetic mapping of
the locus represents an important initial step in the identification of an
X-linked gene implicated in the aetiology of HPC.
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