Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in American men. A family history of prostate cancer is one of the strongest risk factors for the disease. Both epidemiological and segregation analyses confirm that hereditary components are involved in prostate cancer etiology, with inheritance of rare, autosomal dominant alleles thought to explain incidence in some families. We hypothesize that hereditary prostate cancer genes will be localized through analyses of high-risk families with three or more affected first degree relatives, affected men in three generations, or siblings diagnosed at younger ages (<65 years). Towards this end, the Prostate Cancer Genetic Research Study (PROGRESS) has collected baseline data on 152 high-risk families. Using this resource, specific aims to be accomplished as part of this grant are: 1) To extend pedigrees and verify family history of cancer data for families segregating prostate cancer and other cancers, families with five or more living affected men, and non-Caucasian families, 2) To initiate recruitment of new high-risk minority families, particularly African American families, 3) To extend pedigrees and confirm linkage analyses using markers in the region of 1p36, which appears to be the locus for an hereditary prostate cancer gene (CAPB) in families with brain cancer, and, 4) To complete linkage analyses on the 152 families using six markers in the region of 1q24-25, which is the locus for the first hereditary prostate gene (HPC1) to be reported. Epidemiological and clinical data such as age at diagnosis, family cancer history, and tumor stage and grade will be used to stratify families into homogeneous subsets, maximizing power to identify linkage in this complex disease. Finding such linkages and associated genes may provide powerful insights into the underlying genetic defects involved in the development of prostate cancer, including both the hereditary and more common sporadic forms of the disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA080122-05
Application #
6628176
Study Section
Special Emphasis Panel (ZRG4-EDC-2 (02))
Program Officer
Seminara, Daniela
Project Start
1999-04-08
Project End
2004-05-31
Budget Start
2003-02-01
Budget End
2004-05-31
Support Year
5
Fiscal Year
2003
Total Cost
$435,916
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
FitzGerald, L M; Zhao, S; Leonardson, A et al. (2018) Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases. Prostate Cancer Prostatic Dis 21:228-237
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

Showing the most recent 10 out of 28 publications