BACKGROUND: Although the subject of intensive study, the genetic influences responsible for familial clustering of prostate cancer remain largely unidentified. Genome-wide scans for linkage in prostate cancer families can be used to systematically search for genes capable of affecting risk for the disease. METHODS: All available family members from 188 families, each having at least three first-degree relatives affected with prostate cancer, were genotyped at 406 markers distributed across the genome at average intervals of less than 10 cM. Genotype data was analyzed using primarily a non-parametric, multipoint approach, although parametric analyses were performed as well. RESULTS: The strongest evidence for linkage was observed at D4S1615, at 4q21 (LOD of 2.8, P = 0.0002). Two other regions had LOD scores over 2.0: at 9q34 (marker D9S1826, LOD = 2.17, P = 0.0008) and at 2q23 (marker D2S151, LOD = 2.03, P = 0.001). An additional 12 regions had LOD scores over 1.0, including markers at 1q24-25 and 7q22 having scores >1.6. Stratifying the linkage results by age of diagnosis indicated that the linkages to chromosomes 2 and 4 were strongest in families with early and late ages of diagnosis, respectively. CONCLUSIONS: Our data implicate several new loci as harboring prostate cancer susceptibility genes, and provide confirmatory evidence of linkage at several loci identified previously in other genome-wide scans, including the three regions (4q21, 9q34, and 2q23) with strongest evidence for prostate cancer linkage. These data also emphasize the need to combine linkage data from large numbers of prostate cancer families in efforts to effectively address the extensive heterogeneity that characterizes genetic aspects of this disease. Copyright 2003 Wiley-Liss, Inc.
BACKGROUND: Although the subject of intensive study, the genetic influences responsible for familial clustering of prostate cancer remain largely unidentified. Genome-wide scans for linkage in prostate cancer families can be used to systematically search for genes capable of affecting risk for the disease. METHODS: All available family members from 188 families, each having at least three first-degree relatives affected with prostate cancer, were genotyped at 406 markers distributed across the genome at average intervals of less than 10 cM. Genotype data was analyzed using primarily a non-parametric, multipoint approach, although parametric analyses were performed as well. RESULTS: The strongest evidence for linkage was observed at D4S1615, at 4q21 (LOD of 2.8, P = 0.0002). Two other regions had LOD scores over 2.0: at 9q34 (marker D9S1826, LOD = 2.17, P = 0.0008) and at 2q23 (marker D2S151, LOD = 2.03, P = 0.001). An additional 12 regions had LOD scores over 1.0, including markers at 1q24-25 and 7q22 having scores >1.6. Stratifying the linkage results by age of diagnosis indicated that the linkages to chromosomes 2 and 4 were strongest in families with early and late ages of diagnosis, respectively. CONCLUSIONS: Our data implicate several new loci as harboring prostate cancer susceptibility genes, and provide confirmatory evidence of linkage at several loci identified previously in other genome-wide scans, including the three regions (4q21, 9q34, and 2q23) with strongest evidence for prostate cancer linkage. These data also emphasize the need to combine linkage data from large numbers of prostate cancer families in efforts to effectively address the extensive heterogeneity that characterizes genetic aspects of this disease. Copyright 2003 Wiley-Liss, Inc.
Authors: Danielle M Friedrichsen; Janet L Stanford; Sarah D Isaacs; Marta Janer; Bao-Li Chang; Kerry Deutsch; Elizabeth Gillanders; Suzanne Kolb; Katherine E Wiley; Michael D Badzioch; S Lilly Zheng; Patrick C Walsh; Gail P Jarvik; Leroy Hood; Jeffrey M Trent; William B Isaacs; Elaine A Ostrander; Jianfeng Xu Journal: Proc Natl Acad Sci U S A Date: 2004-02-09 Impact factor: 11.205
Authors: Jianfeng Xu; Carl D Langefeld; S Lilly Zheng; Elizabeth M Gillanders; Bao-Li Chang; Sarah D Isaacs; Adrienne H Williams; Kathy E Wiley; Latchezar Dimitrov; Deborah A Meyers; Patrick C Walsh; Jeffrey M Trent; William B Isaacs Journal: Hum Genet Date: 2004-06-05 Impact factor: 4.132
Authors: Bao-Li Chang; Ethan M Lange; Latchezar Dimitrov; Christopher J Valis; Elizabeth M Gillanders; Leslie A Lange; Kathleen E Wiley; Sarah D Isaacs; Fredrik Wiklund; Agnes Baffoe-Bonnie; Carl D Langefeld; S Lilly Zheng; Mika P Matikainen; Tarja Ikonen; Henna Fredriksson; Teuvo Tammela; Patrick C Walsh; Joan E Bailey-Wilson; Johanna Schleutker; Henrik Gronberg; Kathleen A Cooney; William B Isaacs; Edward Suh; Jeffrey M Trent; Jianfeng Xu Journal: Hum Genet Date: 2005-11-23 Impact factor: 4.132
Authors: Ethan M Lange; Jennifer L Beebe-Dimmer; Anna M Ray; Kimberly A Zuhlke; Jaclyn Ellis; Yunfei Wang; Sarah Walters; Kathleen A Cooney Journal: Prostate Date: 2009-03-01 Impact factor: 4.104
Authors: Joan P Breyer; Kate M McReynolds; Brian L Yaspan; Kevin M Bradley; William D Dupont; Jeffrey R Smith Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-06-30 Impact factor: 4.254