Grant Number:	5R01CA068581-04 Interpret this number
Primary Investigator:	Reichardt, Juergen
Organization:	University Of Southern California
Project Title:	5alpha Reductase Genotype, Race and Prostate Cancer Risk
Fiscal Year:	1998

Prostate cancer is diagnosed in almost 200,000 men every year in the US and accounts for about 38,000 annual deaths. In this application, we intend to take a molecular epidemiologic approach to examining our central hypothesis that risk of prostate cancer is substantially influenced by specific genotypes in the human 5alpha-reductase type II (SRD5A2) gene. We propose to investigate the following seven specific aims with molecular genetic and epidemiologic tools: 1) To determine the relationship between the SRD5A2 gene and prostate cancer by genotyping a particular polymorphic DNA marker [TA short tandem repeat (TA-STR)] in the SRD5A2 gene in men with prostate cancer and matched controls from African-American and White men at widely different risks of prostate cancer. 2) To characterize DNA sequence variations in the SRD5A2 gene that predispose men to prostate cancer by sequencing DNA from a small number of African-American and White men with prostate cancer, who carry the high risk SRD5A2 genotypes identified in (1), and so to determine the precise nature of the germline DNA alterations predisposing to prostate cancer. 3) To characterize DNA sequence variations in the SRD5A2 gene that may protect Asian men from prostate cancer by sequencing DNA from a small number of normal (control) Asian men who have low levels of dihydrotestosterone (DHT), and so to determine the germline DNA alterations which may be protective against prostate cancer. 4) To determine the biochemical properties (enzyme activity) of each sequence variation identified in (2) and (3). This will distinguish irrelevant polymorphisms from actual activity altering mutations. 5) To determine the relationship between the SRD5A2 gene and prostate cancer by genotyping [using the relevant sequence variations identified in (4)] the SRD5A2 gene in three racial-ethnic groups [Asian- Americans (defined here as Chinese- and Japanese-Americans), African- Americans and Whites] of prostate cancer cases and matched controls. 6) To utilize the results on the strength of the associations identified in (5) and the prevalence of these alleles in the three racial-ethnic groups, to estimate the contribution of SRD5A2 genotype in explaining the variation in prostate cancer risk among these three groups of men at widely differing risk of prostate cancer. 7) To further characterize the involvement of the SRD5A2 gene in prostate cancer by defining somatic mutations in this gene.




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.
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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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