Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics |
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Authors: | Email author" target="_blank">Daniel?J?SchaidEmail author Investigators of the International Consortium for Prostate Cancer Genetics |
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Institution: | (1) Harwick 7, Mayo Clinic College of Medicine, 200 First ST SW, Rochester, MN 55905, USA |
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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.
The names of all authors and their affiliations are listed in the Acknowledgements. The fact that Dr Schaid’s name is given
here for purposes of correspondence should not be taken to imply that he played the sole leading part in writing this article.
An erratum to this article can be found at |
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