This study is a linkage analysis of families with human prostate cancer. Papers published in Science (1996), Nature Genetics (1998) have shown evidence of prostate cancer susceptibility genes in regions of chromosome 1 and chromosome X. These results have been followed up this year by intensive linkage analyses of additional families to markers in these regions and in other regions that showed some mild evidence of linkage in the initial genome scan. Families have been obtained and genotyped from several regions of the United States, Finland, Iceland and Sweden. Dr. Bailey-Wilson's group is involved in the analyses of the Finnish and Icelandic data. A paper has been published this year in Clinical Cancer Research showing strong evidence for the chromosome X locus but limited evidence for the chromosome 1 locus in our Finnish data. Another paper has been published this year in Human Genetics detailing the linkage results in the Icelandic data. Efforts are also underway to develop additional family resources for this project. These investigators have joined a national Prostate Cancer Linkage Consortium to try to localize prostate cancer loci more rapidly, and a meta-analysis paper from this consortium describing the evidence for linkage to the chromosome 1 locus in a very large comnbined dataset was published in the previous fiscal year. This consortium is now seeking funding to allow genotyping of this large data resource for additional interesting regions that have been implicated as regions of susceptibility loci in prostate cancer. This work will be ongoing. Association analyses have also been performed on additional marker data from Finland, Iceland and the U.S. Paper are currently being prepared detailing the results of these analyses. A linkage genome-wide scan of families from Finland, Sweden, and the U.S., including a significant number of African-American families is ongoing in this fiscal year and will continue into the next year. Preliminary analyses of the Finnish families have been presented at this year's International Congress of Human Genetics and a paper is in preparation. Analyses of the other datasets and of fine mapping data for the Finnish dataset will be ongoing into the next fiscal year.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG000107-05
Application #
6556011
Study Section
(IDRB)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Human Genome Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Gillanders, Elizabeth M; Xu, Jianfeng; Chang, Bao-li et al. (2004) Combined genome-wide scan for prostate cancer susceptibility genes. J Natl Cancer Inst 96:1240-7
Carpten, J; Nupponen, N; Isaacs, S et al. (2002) Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet 30:181-4
Ho, Gloria Y F; Knapp, Michael; Freije, Diha et al. (2002) Transmission/disequilibrium tests of androgen receptor and glutathione S-transferase pi variants in prostate cancer families. Int J Cancer 98:938-42
Rokman, Annika; Ikonen, Tarja; Seppala, Eija H et al. (2002) Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer. Am J Hum Genet 70:1299-304
Baffoe-Bonnie, Agnes B; Kiemeney, Lambertus A L M; Beaty, Terri H et al. (2002) Segregation analysis of 389 Icelandic pedigrees with Breast and prostate cancer. Genet Epidemiol 23:349-63
Xu, Jianfeng; Zheng, S Lilly; Komiya, Akira et al. (2002) Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Nat Genet 32:321-5
Stephan, Dietrich A; Howell, Gareth R; Teslovich, Tanya M et al. (2002) Physical and transcript map of the hereditary prostate cancer region at xq27. Genomics 79:41-50
Powell, I J; Carpten, J; Dunston, G et al. (2001) African-American heredity prostate cancer study: a model for genetic research. J Natl Med Assoc 93:120-3
Verhage, B A; Baffoe-Bonnie, A B; Baglietto, L et al. (2001) Autosomal dominant inheritance of prostate cancer: a confirmatory study. Urology 57:97-101
Powell, I J; Carpten, J; Dunston, G et al. (2001) African-American heredity prostate cancer study: a model for genetic research. J Natl Med Assoc 93:25S-28S

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