BACKGROUND: The aggregation of prostate cancer within families suggests a major inherited component to the disease. Genetic linkage studies have identified several chromosomal regions that may contain prostate cancer susceptibility loci, but none has been definitively implicated. METHODS: We performed a genome-wide linkage search based on 64 families, 63 with at least 3 cases of prostate cancer, ascertained in five countries. The majority of cases from these centers presented with clinically detected disease. Four hundred and one polymorphic markers were typed in 268 individuals. Multipoint heterogeneity analysis was conducted under three models of susceptibility; non-parametric analyses were also performed. RESULTS: Some weak evidence of linkage, under at least one of the genetic models, was observed to markers on chromosomes 2 (heterogeneity LOD (HLOD) = 1.15, P = 0.021), 3 (HLOD = 1.25, P = 0.016), 4 (HLOD = 1.28, P = 0.015), 5 (HLOD = 1.20, P = 0.019), 6 (HLOD = 1.41, P = 0.011), and 11 (HLOD = 1.24, P = 0.018), and in two regions on chromosome 18 (HLOD = 1.40, P = 0.011 and HLOD = 1.34, P = 0.013). There were no HLOD scores greater than 1.5 under any model, and no locus would be predicted to explain more than half of the genetic effect. No evidence in favor of linkage to previously suggested regions on chromosomes 1, 8, 17, 20, or X was found. CONCLUSIONS: Genetic susceptibility to prostate cancer is likely to be controlled by many loci, with no single gene explaining a large fraction of the familial risk. Pooling of results from all available genome scans is likely to be required to obtain definitive linkage results. Copyright 2003 Wiley-Liss, Inc.
BACKGROUND: The aggregation of prostate cancer within families suggests a major inherited component to the disease. Genetic linkage studies have identified several chromosomal regions that may contain prostate cancer susceptibility loci, but none has been definitively implicated. METHODS: We performed a genome-wide linkage search based on 64 families, 63 with at least 3 cases of prostate cancer, ascertained in five countries. The majority of cases from these centers presented with clinically detected disease. Four hundred and one polymorphic markers were typed in 268 individuals. Multipoint heterogeneity analysis was conducted under three models of susceptibility; non-parametric analyses were also performed. RESULTS: Some weak evidence of linkage, under at least one of the genetic models, was observed to markers on chromosomes 2 (heterogeneity LOD (HLOD) = 1.15, P = 0.021), 3 (HLOD = 1.25, P = 0.016), 4 (HLOD = 1.28, P = 0.015), 5 (HLOD = 1.20, P = 0.019), 6 (HLOD = 1.41, P = 0.011), and 11 (HLOD = 1.24, P = 0.018), and in two regions on chromosome 18 (HLOD = 1.40, P = 0.011 and HLOD = 1.34, P = 0.013). There were no HLOD scores greater than 1.5 under any model, and no locus would be predicted to explain more than half of the genetic effect. No evidence in favor of linkage to previously suggested regions on chromosomes 1, 8, 17, 20, or X was found. CONCLUSIONS: Genetic susceptibility to prostate cancer is likely to be controlled by many loci, with no single gene explaining a large fraction of the familial risk. Pooling of results from all available genome scans is likely to be required to obtain definitive linkage results. Copyright 2003 Wiley-Liss, Inc.
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: Jianfeng Xu; Latchezar Dimitrov; Bao-Li Chang; Tamara S Adams; Aubrey R Turner; Deborah A Meyers; Rosalind A Eeles; Douglas F Easton; William D Foulkes; Jacques Simard; Graham G Giles; John L Hopper; Lovise Mahle; Pal Moller; Tim Bishop; Chris Evans; Steve Edwards; Julia Meitz; Sarah Bullock; Questa Hope; Chih-Lin Hsieh; Jerry Halpern; Raymond N Balise; Ingrid Oakley-Girvan; Alice S Whittemore; Charles M Ewing; Marta Gielzak; Sarah D Isaacs; Patrick C Walsh; Kathleen E Wiley; William B Isaacs; Stephen N Thibodeau; Shannon K McDonnell; Julie M Cunningham; Katherine E Zarfas; Scott Hebbring; Daniel J Schaid; Danielle M Friedrichsen; Kerry Deutsch; Suzanne Kolb; Michael Badzioch; Gail P Jarvik; Marta Janer; Leroy Hood; Elaine A Ostrander; Janet L Stanford; Ethan M Lange; Jennifer L Beebe-Dimmer; Caroline E Mohai; Kathleen A Cooney; Tarja Ikonen; Agnes Baffoe-Bonnie; Henna Fredriksson; Mika P Matikainen; Teuvo Lj Tammela; Joan Bailey-Wilson; Johanna Schleutker; Christiane Maier; Kathleen Herkommer; Josef J Hoegel; Walther Vogel; Thomas Paiss; Fredrik Wiklund; Monica Emanuelsson; Elisabeth Stenman; Bjorn-Anders Jonsson; Henrik Gronberg; Nicola J Camp; James Farnham; Lisa A Cannon-Albright; Daniela Seminara Journal: Am J Hum Genet Date: 2005-06-29 Impact factor: 11.025
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Authors: Nicola J Camp; Lisa A Cannon-Albright; James M Farnham; Agnes B Baffoe-Bonnie; Asha George; Isaac Powell; Joan E Bailey-Wilson; John D Carpten; Graham G Giles; John L Hopper; Gianluca Severi; Dallas R English; William D Foulkes; Lovise Maehle; Pal Moller; Ros Eeles; Douglas Easton; Michael D Badzioch; Alice S Whittemore; Ingrid Oakley-Girvan; Chih-Lin Hsieh; Latchezar Dimitrov; Jianfeng Xu; Janet L Stanford; Bo Johanneson; Kerry Deutsch; Laura McIntosh; Elaine A Ostrander; Kathleen E Wiley; Sarah D Isaacs; Patrick C Walsh; Stephen N Thibodeau; Shannon K McDonnell; Scott Hebbring; Daniel J Schaid; Ethan M Lange; Kathleen A Cooney; Teuvo L J Tammela; Johanna Schleutker; Thomas Paiss; Christiane Maier; Henrik Grönberg; Fredrik Wiklund; Monica Emanuelsson; William B Isaacs Journal: Hum Mol Genet Date: 2007-05-03 Impact factor: 6.150
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