Grant Number:	1R01CA094211-01A1 Interpret this number
Primary Investigator:	Witte, John
Organization:	Case Western Reserve University
Project Title:	Androgen Pathway Factors and Prostate Cancer
Fiscal Year:	2002

DESCRIPTION (provided by applicant): Prostate cancer is a common, but complex disease. Risk factors for this disease are not yet fully understood, but may involve both genetic and environmental influences. These factors may act alone, or in combination, to increase risk of prostate cancer. Some of the most promising potential risk factors are those involved with androgen metabolism, which drives prostate cell growth and differentiation. Therefore, in the following specific aims we propose an epidemiologic study of the relation between prostate cancer and two factors that may affect the androgen metabolism pathway: candidate genes and dietary fat. Specific Aim 1. Our first aim is to investigate the impact of novel or little studied polymorphisms in the following ten androgen pathway candidate genes on prostate cancer risk: 1) CYP3A4; 2) 5a-reductase II; 3) CYP1 7; 4) the Androgen Receptor; 5) Kallikrein 3; 6) 3Beta-hydroxysteroid dehydrogenase II; 7) CYP1 la; 8) CYP19; 9) Insulin-like Growth Factor-I; and 10) CYP1B1 Specific Aim 2. This aim will expand our consideration of the androgen pathway by investigating the relation between prostate cancer risk and consumption of polyunsaturated dietary fat, and the polyunsaturated fatty acids linoleic acid and alpha-linoleic acid. Specific Aim 3. Our third aim is to synthesize the information on candidate genes and dietary fats studied here by looking at their joint and interactive effects on prostate cancer risk. We will use both a conventional analysis, and a hierarchical modeling approach, which will attempt to improve our estimates of risk by incorporating into the analysis biologic information about the affect of these candidate genes and dietary fat on the androgen pathway. To fulfill these specific aims, we will use existing information from a sibling-based study of 455 cases and 488 controls Our comprehensive evaluation of androgen pathway factors should help clarify the impact of these genetic and dietary factors on prostate cancer. Ultimately, findings from such work will help lead to individualized screening that expressly reflects a man's risk of prostate cancer.




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Copy number alterations in prostate tumors and disease aggressiveness.
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Fine-mapping of prostate cancer aggressiveness loci on chromosome 7q22-35.
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Prostate cancer susceptibility variants confer increased risk of disease progression.
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Dietary omega-3 fatty acids, cyclooxygenase-2 genetic variation, and aggressive prostate cancer risk.
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Carboxypeptidase 4 gene variants and early-onset intermediate-to-high risk prostate cancer.
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Omega-3 fatty acids, genetic variants in COX-2 and prostate cancer.
Authors: Reese A.C. , Fradet V. , Witte J.S. .
Source: Journal Of Nutrigenetics And Nutrigenomics, 2009; 2(3), p. 149-58.
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8q24 and prostate cancer: association with advanced disease and meta-analysis.
Authors: Cheng I. , Plummer S.J. , Jorgenson E. , Liu X. , Rybicki B.A. , Casey G. , Witte J.S. .
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COX2 genetic variation, NSAIDs, and advanced prostate cancer risk.
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Trans-fatty acid intake and increased risk of advanced prostate cancer: modification by RNASEL R462Q variant.
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MIC1 and IL1RN genetic variation and advanced prostate cancer risk.
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Association of testis derived transcript gene variants and prostate cancer risk.
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Toll-like receptor 4 genetic variation and advanced prostate cancer risk.
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An empirical evaluation of the common disease-common variant hypothesis.
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Vitamin D receptor genotypes/haplotypes and prostate cancer risk.
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Nonsteroidal antiinflammatory drugs and decreased risk of advanced prostate cancer: modification by lymphotoxin alpha.
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Coverage and power in genomewide association studies.
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Podocalyxin variants and risk of prostate cancer and tumor aggressiveness.
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Relationship between body size and prostate cancer in a sibling based case-control study.
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No association between genetic polymorphisms in insulin and insulin receptor substrate-1 and prostate cancer.
Authors: Li L. , Cicek M.S. , Casey G. , Witte J.S. .
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Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11alpha in prostate cancer risk and aggressiveness.
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No association between a tetranucleotide repeat polymorphism of CYP19 and prostate cancer.
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CYP3A4 and CYP3A5 genotypes, haplotypes, and risk of prostate cancer.
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Haplotype tagging single nucleotide polymorphisms and association studies.
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