This application by Stephen N. Thibodeau entitled """"""""Localization of susceptibility loci in prostate cancer"""""""" seeks funding to support a three-part study to identify genes responsible for prostate cancer predisposition. The study proposes a genome-wide search by microsatellite polymorphism in families with three or four members affected by prostate cancer. These families have been ascertained from the Mayo Clinic Registry of Radical Prostatectomy, comprising approximately 5,500 men who were treated with radical prostatectomy since 1967. As a result of initial evaluation of this registry, 60 kindreds with three or more living affected men (200 sib pairs) have been identified so far as potential subjects for this study. Initial screening by full genome analysis using markers separated by approximately 10 centimorgans will be conducted. Data will be analyzed by both conventional parametric linkage analysis and by affected sib pair approaches. Regions of the genome harboring known or suspected candidate genes for familial prostate cancer or those regions showing elevated LOH in prostate tumor progression (as determined in preliminary studies by the applicant and by other published studies) will be targeted first. Regions identified as potential candidates will be evaluated more closely by refined linkage mapping using additional markers from the region, by physical mapping, and by positional cloning within the regions of interest. Candidate genes within these regions will ultimately be evaluated using conventional approaches for candidate gene analysis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA072818-03
Application #
2837716
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Seminara, Daniela
Project Start
1996-12-26
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb et al. (2016) Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. Nat Commun 7:10979
Southey, Melissa C (see original citation for additional authors) (2016) PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. J Med Genet 53:800-811
Szulkin, Robert; Karlsson, Robert; Whitington, Thomas et al. (2015) Genome-wide association study of prostate cancer-specific survival. Cancer Epidemiol Biomarkers Prev 24:1796-800
Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I et al. (2014) A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet 46:1103-9
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
Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G et al. (2011) Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat Genet 43:785-91
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
Schaid, Daniel J; McDonnell, Shannon K; Riska, Shaun M et al. (2010) Estimation of genotype relative risks from pedigree data by retrospective likelihoods. Genet Epidemiol 34:287-98

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