Evidence for a prostate cancer susceptibility locus on the X chromosome

Jianfeng Xu, Deborah Meyers, Diha Freije, Sarah Isaacs, Kathy Wiley, Deborah Nusskern, Charles Ewing, Eric Wilkens, Piroska Bujnovszky, G. Steven Bova, Patrick Walsh, William Isaacs, Johanna Schleutker, Mika Matikainen, Teuvo Tammela, Tapio Visakorpi, Olli P. Kallioniemi, Rebecca Berry, Daniel Schaid, Amy FrenchShannon McDonnell, Jennifer Schroeder, Michael Blute, Stephen Thibodeau, Henrik Grönberg, Monika Emanuelsson, Jan Erik Damber, Anders Bergh, Björn Anders Jonsson, Jeffrey Smith, Joan Bailey-Wilson, John Carpten, Dietrich Stephan, Elizabeth Gillanders, Isaac Amundson, Tommi Kainu, Diana Freas-Lutz, Agnes Baffoe-Bonnie, Anne Van Aucken, Raman Sood, Francis Collins, Michael Brownstein, Jeffrey Trent

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368 Scopus citations

Abstract

Over 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 annually. 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, θ=0.26, in the combined data set. Parametric multi point and non-parametric analyses provided results consistent with the two-point analysis. Significant 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.

Original languageEnglish (US)
Pages (from-to)175-179
Number of pages5
JournalNature Genetics
Volume20
Issue number2
DOIs
StatePublished - Oct 15 1998

ASJC Scopus subject areas

  • Genetics

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    Xu, J., Meyers, D., Freije, D., Isaacs, S., Wiley, K., Nusskern, D., Ewing, C., Wilkens, E., Bujnovszky, P., Steven Bova, G., Walsh, P., Isaacs, W., Schleutker, J., Matikainen, M., Tammela, T., Visakorpi, T., Kallioniemi, O. P., Berry, R., Schaid, D., ... Trent, J. (1998). Evidence for a prostate cancer susceptibility locus on the X chromosome. Nature Genetics, 20(2), 175-179. https://doi.org/10.1038/2477