| Literature DB >> 16932970 |
Daniel J Schaid1, Shannon K McDonnell, Katherine E Zarfas, Julie M Cunningham, Scott Hebbring, Stephen N Thibodeau, Rosalind A Eeles, Douglas F Easton, William D Foulkes, Jacques Simard, Graham G Giles, John L Hopper, Lovise Mahle, Pal Moller, Michael Badzioch, D Timothy Bishop, Chris Evans, Steve Edwards, Julia Meitz, Sarah Bullock, Questa Hope, Michelle Guy, Chih-lin Hsieh, Jerry Halpern, Raymond R Balise, Ingrid Oakley-Girvan, Alice S Whittemore, Jianfeng Xu, Latchezar Dimitrov, Bao-Li Chang, Tamara S Adams, Aubrey R Turner, Deborah A Meyers, Danielle M Friedrichsen, Kerry Deutsch, Suzanne Kolb, Marta Janer, Leroy Hood, Elaine A Ostrander, Janet L Stanford, Charles M Ewing, Marta Gielzak, Sarah D Isaacs, Patrick C Walsh, Kathleen E Wiley, William B Isaacs, Ethan M Lange, Lindsey A Ho, Jennifer L Beebe-Dimmer, David P Wood, Kathleen A Cooney, Daniela Seminara, Tarja Ikonen, Agnes Baffoe-Bonnie, Henna Fredriksson, Mika P Matikainen, Teuvo L J Tammela, Joan Bailey-Wilson, Johanna Schleutker, Christiane Maier, Kathleen Herkommer, Josef J Hoegel, Walther Vogel, Thomas Paiss, Fredrik Wiklund, Monica Emanuelsson, Elisabeth Stenman, Björn-Anders Jonsson, Henrik Grönberg, Nicola J Camp, James Farnham, Lisa A Cannon-Albright, William J Catalona, Brian K Suarez, Kimberly A Roehl.
Abstract
While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families. Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1-14.3 (LOD = 2.4), and 20p11.21-q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11, LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13-22.3; LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical utility for men with aggressive prostate cancer and their relatives.Entities:
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Year: 2006 PMID： 16932970 DOI： 10.1007/s00439-006-0219-9
Source DB: PubMed Journal: Hum Genet ISSN： 0340-6717 Impact factor: 4.132