This proposal is a competitive renewal for the grant entitled, """"""""Genetic Epidemiology of Prostate Cancer"""""""" The project involves a multidisciplinary group of researchers working on The Prostate Cancer Genetic Research Study (PROGRESS), an investigation of high-risk prostate cancer families aimed at mapping loci for the hereditary form of this disease. In addition, the study aims to further knowledge of the genetic epidemiology and molecular biology of prostate cancer. During the grant period covered by this continuation, we will utilize baseline and follow-up survey data, medical records, genotyping data, and DNA samples from members of PROGRESS families to address the following primary aims: 1) To complete linkage analyses of 421 genome-wide markers in 255 hereditary prostate cancer (HPC) families stratified by the presence of other primary cancers in the family; 2) To complete linkage and regression analyses of 421 genome-wide markers in 255 PROGRESS families, incorporating clinical data to search for loci associated with more aggressive phenotypes; 3) To genotype selected PROGRESS families for mutations in the BRCA2 gene to determine the role of such mutations in HPC; and, 4) To continue follow-up of members of 271 HPC families, with expansion of pedigrees and data collection as men newly diagnosed with prostate cancer are identified. In addition to the primary aims, we will address the following secondary aims: 5) To continue recruitment of African American families with prostate cancer; and, 6) To evaluate knowledge of and interest in genetic testing among affected and unaffected men. Genomic scan data, family cancer history data, and clinical data on prostate cases will be available. These data will be used to stratify families into more homogeneous subgroups for linkage analyses and to incorporate such data into regression models as quantitative traits. These approaches may lead to identification of new loci for HPC, including those linked to more aggressive disease. PROGRESS is a unique resource for addressing these aims and represents one of the largest collections of HPC families in the world. Finding such linkages and associated genes may provide novel and important insights into the underlying genetic epidemiology of prostate cancer, including the hereditary and sporadic forms of this common and complex disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA080122-10
Application #
7434511
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Seminara, Daniela
Project Start
1999-04-08
Project End
2012-05-31
Budget Start
2008-06-01
Budget End
2012-05-31
Support Year
10
Fiscal Year
2008
Total Cost
$423,798
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Karyadi, Danielle M; Geybels, Milan S; Karlins, Eric et al. (2017) Whole exome sequencing in 75 high-risk families with validation and replication in independent case-control studies identifies TANGO2, OR5H14, and CHAD as new prostate cancer susceptibility genes. Oncotarget 8:1495-1507
Karyadi, Danielle M; Zhao, Shanshan; He, Qianchuan et al. (2015) Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families. Int J Cancer 136:2166-71
Bailey-Wilson, Joan E; Childs, Erica J; Cropp, Cheryl D et al. (2012) Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families. BMC Med Genet 13:46
Lu, Lingyi; Cancel-Tassin, Geraldine; Valeri, Antoine et al. (2012) Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG. Prostate 72:410-26
Johanneson, Bo; McDonnell, Shannon K; Karyadi, Danielle M et al. (2010) Family-based association analysis of 42 hereditary prostate cancer families identifies the Apolipoprotein L3 region on chromosome 22q12 as a risk locus. Hum Mol Genet 19:3852-62
Christensen, G Bryce; Baffoe-Bonnie, Agnes B; George, Asha et al. (2010) Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics using novel sumLINK and sumLOD analyses. Prostate 70:735-44
Harris, Julie N; Bowen, Deborah J; Kuniyuki, Alan et al. (2009) Interest in genetic testing among affected men from hereditary prostate cancer families and their unaffected male relatives. Genet Med 11:344-55
Stanford, Janet L; FitzGerald, Liesel M; McDonnell, Shannon K et al. (2009) Dense genome-wide SNP linkage scan in 301 hereditary prostate cancer families identifies multiple regions with suggestive evidence for linkage. Hum Mol Genet 18:1839-48
Agalliu, Ilir; Suuriniemi, Miia; Prokunina-Olsson, Ludmila et al. (2008) Evaluation of a variant in the transcription factor 7-like 2 (TCF7L2) gene and prostate cancer risk in a population-based study. Prostate 68:740-7

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