Evidence for a prostate cancer susceptibility locus on the X chromosome

• Published in: Nature genetics Vol. 20; no. 2; pp. 175 - 179
• Main Authors: Xu, Jianfeng, Meyers, Deborah, Freije, Diha, Isaacs, Sarah, Wiley, Kathy, Nusskern, Deborah, Ewing, Charles, Wilkens, Eric, Bujnovszky, Piroska, Bova, G. Steven, Walsh, Patrick, Isaacs, William, Schleutker, Johanna, Matikainen, Mika, Tammela, Teuvo, Visakorpi, Tapio, Kallioniemi, Olli-P, Berry, Rebecca, Schaid, Daniel, French, Amy, McDonnell, Shannon, Schroeder, Jennifer, Blute, Michael, Thibodeau, Stephen, Grönberg, Henrik, Emanuelsson, Monika, Damber, Jan-Erik, Bergh, Anders, Jonsson, Björn-Anders, Smith, Jeffrey, Bailey-Wilson, Joan, Carpten, John, Stephan, Dietrich, Gillanders, Elizabeth, Amundson, Isaac, Kainu, Tommi, Freas-Lutz, Diana, Baffoe-Bonnie, Agnes, Van Aucken, Anne, Sood, Raman, Collins, Francis, Brownstein, Michael, Trent, Jeffrey
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-10-1998
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Chromosome Mapping; Genetic Markers; Genetic Predisposition to Disease - genetics; Genotype; Gynecology. Andrology. Obstetrics; Humans; Lod Score; Male; Male genital diseases; Medical sciences; Middle Aged; Pedigree; Prostatic Neoplasms - genetics; Receptors, Androgen - genetics; Tumors; X Chromosome; Genetic mapping; Human; Sex linked character; Linkage; Prostate disease; Genetic disease; Risk factor; Predisposition; Tumor; X-Chromosome; Genetic association; Male genital diseases; Prostate
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/2477

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, theta=0.26, in the combined data set. Parametric multipoint 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.