Grant Number:	2R01CA068581-05 Interpret this number
Primary Investigator:	Reichardt, Juergen
Organization:	University Of Southern California
Project Title:	5 Alpha Reductase Genotype, Race Prostate Cancer Risk
Fiscal Year:	1999

DESCRIPTION: (Adapted from the Investigator's Abstract) Prostate cancer is currently the most common cancer among American men. Regulation of prostatic cell growth is largely controlled by androgens including especially dihydrotestosterone (DHT). This compound is synthesized from the male hormone testosterone by the enzyme 5-alpha reductase which is encoded in the prostate by the SRD5A2 gene. The etiology of prostate cancer appears to include increased steroid 5-alpha reductase activity particularly across racial/ethnic groups which are at very different risk for prostate cancer, such as high-risk African-Americans and lower risk Asians, the two extreme groups for risk. We have identified and characterized genetic variability in the SRD5A2 gene among various racial/ethnic groups in the US and between prostate cancer cases and controls. These investigations made use of a large multiethnic cohort in Los Angeles and Hawaii. We propose to build on and expand our studies of the SRD5A2 gene and prostate cancer by epidemiologic, genetic and biochemical methods. It is our overall hypothesis that genetic variation at the SRD5A2 locus plays a significant role in predisposition to and progression of prostate cancer and in explaining the racial/ethnic variation of risk. To this end, we intend to investigate the following interrelated six specific aims: 1) To identify all constitutional ("germline") DNA variations across the entire SRD5A2 gene that might contribute to predisposition to prostate cancer; 2) To determine the relationship between each variant identified in Specific Aim 1 to prostate cancer risk in for racial/ethnic populations: 4) To identify somatic mutations in the SRD5A2 gene involved in prostate cancer progression; 5) To characterize the biochemical properties of the somatic DNA genetic variants identified in Specific aims 1 and 4 in an in vitro model system; 6) To determine the contribution of somatic DNA genetic variants in the SRD5A2 gene to prostate cancer progression within and across racial/ethnic groups. Therefore, we will investigate the molecular basis of predisposition to prostate cancer and its progression in a multidisciplinary study rooted in molecular epidemiology with significant implications for presymptomatic identification of at-risk individuals, targeted chemoprevention and improved treatment of this disease.




No association between the SRD5A2 gene A49T missense variant and prostate cancer risk: lessons learned.
Authors: Pearce C.L. , Van Den Berg D.J. , Makridakis N. , Reichardt J.K. , Ross R.K. , Pike M.C. , Kolonel L.N. , Henderson B.E. .
Source: Human Molecular Genetics, 2008-08-15 00:00:00.0; 17(16), p. 2456-61.
EPub date: 2008-08-15 00:00:00.0.
PMID: 18469342
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A renaissance of "biochemical genetics"? SNPs, haplotypes, function, and complex diseases.
Authors: Mehrian-Shai R. , Reichardt J.K. .
Source: Molecular Genetics And Metabolism, 2004 Sep-Oct; 83(1-2), p. 47-50.
PMID: 15464419
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Pharmacogenetics of human androgens and prostate cancer--an update.
Authors: Novelli G. , Margiotti K. , Chiocca A.M. , Spera E. , Micali F. , Reichardt J.K. .
Source: Pharmacogenomics, 2004 Apr; 5(3), p. 283-94.
PMID: 15102543
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Molecular epidemiology of androgen-metabolic loci in prostate cancer: predisposition and progression.
Authors: Makridakis N.M. , Reichardt J.K. .
Source: The Journal Of Urology, 2004 Feb; 171(2 Pt 2), p. S25-8; discussion S28-9.
PMID: 14713749
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Association between two polymorphisms in the SRD5A2 gene and serum androgen concentrations in British men.
Authors: Allen N.E. , Reichardt J.K. , Nguyen H. , Key T.J. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2003 Jun; 12(6), p. 578-81.
PMID: 12815006
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Steroid 5-alpha reductase type II V89L substitution is not associated with risk of prostate cancer in a multiethnic population study.
Authors: Pearce C.L. , Makridakis N.M. , Ross R.K. , Pike M.C. , Kolonel L.N. , Henderson B.E. , Reichardt J.K. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2002 Apr; 11(4), p. 417-8.
PMID: 11927504
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Multiplex Automated Primer Extension Analysis: Simultaneous Genotyping Of Several Polymorphisms
Authors: Makridakis N.M. , Reichardt J.K. .
Source: Biotechniques, 2001 Dec; 31(6), p. 1374-80.
PMID: 11768667
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Polymorphic Markers In The Srd5a2 Gene And Prostate Cancer Risk: A Population-based Case-control Study
Authors: Hsing A.W. , Chen C. , Chokkalingam A.P. , Gao Y.T. , Dightman D.A. , Nguyen H.T. , Deng J. , Cheng J. , Sesterhenn I.A. , Mostofi F.K. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2001 Oct; 10(10), p. 1077-82.
PMID: 11588134
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Pharmacogenetics of human androgens and prostatic diseases.
Authors: Novelli G. , Margiotti K. , Sangiuolo F. , Reichardt J.K. .
Source: Pharmacogenomics, 2001 Feb; 2(1), p. 65-72.
PMID: 11258198
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Molecular epidemiology of hormone-metabolic loci in prostate cancer.
Authors: Makridakis N.M. , Reichardt J.K. .
Source: Epidemiologic Reviews, 2001; 23(1), p. 24-9.
PMID: 11588850
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Biochemical And Pharmacogenetic Dissection Of Human Steroid 5 Alpha-reductase Type Ii
Authors: Makridakis N.M. , di Salle E. , Reichardt J.K. .
Source: Pharmacogenetics, 2000 Jul; 10(5), p. 407-13.
PMID: 10898110
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Evidence For An Association Between The Srd5a2 (type Ii Steroid 5 Alpha-reductase) Locus And Prostate Cancer In Italian Patients
Authors: Margiotti K. , Sangiuolo F. , De Luca A. , Froio F. , Pearce C.L. , Ricci-Barbini V. , Micali F. , Bonafe M. , Franceschi C. , Dallapiccola B. , et al. .
Source: Disease Markers, 2000; 16(3-4), p. 147-50.
PMID: 11381197
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A Reliable Pcr Amplification Method For Microdissected Tumor Cells Obtained From Paraffin-embedded Tissue
Authors: Akalu A. , Reichardt J.K. .
Source: Genetic Analysis : Biomolecular Engineering, 1999-12-15 00:00:00.0; 15(6), p. 229-33.
PMID: 10609759
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Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA.
Authors: Makridakis N.M. , Ross R.K. , Pike M.C. , Crocitto L.E. , Kolonel L.N. , Pearce C.L. , Henderson B.E. , Reichardt J.K. .
Source: Lancet (london, England), 1999-09-18 00:00:00.0; 354(9183), p. 975-8.
PMID: 10501358
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Gen Gen: The Genomic Genetic Analysis Of Androgen-metabolic Genes And Prostate Cancer As A Paradigm For The Dissection Of Complex Phenotypes
Authors: Reichardt J.K. .
Source: Frontiers In Bioscience : A Journal And Virtual Library, 1999-07-15 00:00:00.0; 4, p. D596-600.
PMID: 10417059
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Somatic Mutations At The Srd5a2 Locus Encoding Prostatic Steroid 5alpha-reductase During Prostate Cancer Progression
Authors: Akalu A. , Dlmajian D.A. , Highshaw R.A. , Nichols P.W. , Reichardt J.K. .
Source: The Journal Of Urology, 1999 Apr; 161(4), p. 1355-8.
PMID: 10081907
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Sex steroid hormones and genetic susceptibility to breast and prostate cancer.
Authors: Feigelson H.S. , Ross R.K. , Yu M.C. , Coetzee G.A. , Reichardt J.K. , Henderson B.E. .
Source: Drug Metabolism Reviews, 1998 May; 30(2), p. 421-34.
PMID: 9606611
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A Prevalent Missense Substitution That Modulates Activity Of Prostatic Steroid 5alpha-reductase
Authors: Makridakis N. , Ross R.K. , Pike M.C. , Chang L. , Stanczyk F.Z. , Kolonel L.N. , Shi C.Y. , Yu M.C. , Henderson B.E. , Reichardt J.K. .
Source: Cancer Research, 1997-03-15 00:00:00.0; 57(6), p. 1020-2.
PMID: 9067262
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Genetic susceptibility to cancer from exogenous and endogenous exposures.
Authors: Feigelson H.S. , Ross R.K. , Yu M.C. , Coetzee G.A. , Reichardt J.K. , Henderson B.E. .
Source: Journal Of Cellular Biochemistry. Supplement, 1996; 25, p. 15-22.
PMID: 9027593
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