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Grant Details

Grant Number: 5R01CA068578-05 Interpret this number
Primary Investigator: Spitz, Margaret
Organization: University Of Texas Md Anderson Can Ctr
Project Title: Environmental & Genetic Determinants of Prostate Cancer
Fiscal Year: 1999


Abstract

A critical goal in prostate cancer (PC) epidemiology is identifying the biological mechanism underlying the progression from clinically non- significant PC to clinically relevant PC. We propose to conduct a case- case study comparing a group of 100 men with non-significant PC and an age- and ethnic-matched group of 300 men with clinically relevant PC. These two groups will be characterized by comprehensive epidemiologic profiles and by comparison of multiple genetic alterations in their PC lesions. The objective is to identify environmental and genetic determinants of PC progression. The long term goal is to identify and clone a tumor suppressor gene (rSG), frequently inactivated in PC, that might be a future target for therapy. The hypothesis being tested is that foci of preneoplasia or low grade cancer have experienced some, but not all, the necessary steps to progress to invasive cancer, and that environmental and genetic factors play a role in this progression. The epidemiologic component will compare risk profiles of men with respect to previously reported and putative risk factors (including dietary intake of total fat, fatty acids, and micronutrients, sociodemographic factors, patterns of body fat distribution, vasectomy, family history and male patterns of balding). The working hypotheses are that environmental factors play a role in the development of the aggressive phenotype. The molecular genetic component will focus on analysis of allele loss in the two groups of men by screening all available paired specimens of PC and normal tissues and/or preneoplastic lesions such as prostatic intraepithelial neoplasia. The working hypothesis is that frequent LOH at specific chromosomal regions,which is associated with inactivation of tumor suppressor genes, is a major mechanism in the progression of PC and that non-significant PC can be distinguished from clinical PC on the basis of genetic changes. Our goal is to identify new molecular genetic markers, highly associated with the progression of PC, and that can be used as diagnostic and prognostic markers. In addition, this component will focus on limiting chromosomal regions which show frequent LOH/deletions to a specific chromosomal band or sub-bands by generating new polymorphic microsatellite probes from microdissected chromosomal regions. The presence of lesions of unknown malignant potential poses a serious therapeutic dilemma. Environmental factors in concert with genetic alterations such as frequent LOH at specific chromosomal regions may be important mechanisms in the progression of PC and may be of predictive and therapeutic value.



Publications

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.
Authors: Rand K.A. , Song C. , Dean E. , Serie D.J. , Curtin K. , Sheng X. , Hu D. , Huff C.A. , Bernal-Mizrachi L. , Tomasson M.H. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016 12; 25(12), p. 1609-1618.
EPub date: 2016-09-01.
PMID: 27587788
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Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.
Authors: Han Y. , Rand K.A. , Hazelett D.J. , Ingles S.A. , Kittles R.A. , Strom S.S. , Rybicki B.A. , Nemesure B. , Isaacs W.B. , Stanford J.L. , et al. .
Source: Journal of the National Cancer Institute, 2016 Jul; 108(7), .
EPub date: 2016-01-27.
PMID: 26823525
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Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.
Authors: Rand K.A. , Rohland N. , Tandon A. , Stram A. , Sheng X. , Do R. , Pasaniuc B. , Allen A. , Quinque D. , Mallick S. , et al. .
Source: Human molecular genetics, 2016-01-15; 25(2), p. 371-81.
EPub date: 2015-11-24.
PMID: 26604137
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Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.
Authors: Han Y. , Hazelett D.J. , Wiklund F. , Schumacher F.R. , Stram D.O. , Berndt S.I. , Wang Z. , Rand K.A. , Hoover R.N. , Machiela M.J. , et al. .
Source: Human molecular genetics, 2015-10-01; 24(19), p. 5603-18.
EPub date: 2015-07-10.
PMID: 26162851
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Generalizability of established prostate cancer risk variants in men of African ancestry.
Authors: Han Y. , Signorello L.B. , Strom S.S. , Kittles R.A. , Rybicki B.A. , Stanford J.L. , Goodman P.J. , Berndt S.I. , Carpten J. , Casey G. , et al. .
Source: International journal of cancer, 2015-03-01; 136(5), p. 1210-7.
EPub date: 2014-07-15.
PMID: 25044450
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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Authors: Al Olama A.A. , Kote-Jarai Z. , Berndt S.I. , Conti D.V. , Schumacher F. , Han Y. , Benlloch S. , Hazelett D.J. , Wang Z. , Saunders E. , et al. .
Source: Nature genetics, 2014 Oct; 46(10), p. 1103-9.
EPub date: 2014-09-14.
PMID: 25217961
Related Citations

A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Authors: Monda K.L. , Chen G.K. , Taylor K.C. , Palmer C. , Edwards T.L. , Lange L.A. , Ng M.C. , Adeyemo A.A. , Allison M.A. , Bielak L.F. , et al. .
Source: Nature genetics, 2013 Jun; 45(6), p. 690-6.
EPub date: 2013-04-14.
PMID: 23583978
Related Citations

Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
Authors: Liu C.T. , Monda K.L. , Taylor K.C. , Lange L. , Demerath E.W. , Palmas W. , Wojczynski M.K. , Ellis J.C. , Vitolins M.Z. , Liu S. , et al. .
Source: PLoS genetics, 2013; 9(8), p. e1003681.
EPub date: 2013-08-15.
PMID: 23966867
Related Citations

Global patterns of prostate cancer incidence, aggressiveness, and mortality in men of african descent.
Authors: Rebbeck T.R. , Devesa S.S. , Chang B.L. , Bunker C.H. , Cheng I. , Cooney K. , Eeles R. , Fernandez P. , Giri V.N. , Gueye S.M. , et al. .
Source: Prostate cancer, 2013; 2013, p. 560857.
EPub date: 2013-02-13.
PMID: 23476788
Related Citations

Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
Authors: N'Diaye A. , Chen G.K. , Palmer C.D. , Ge B. , Tayo B. , Mathias R.A. , Ding J. , Nalls M.A. , Adeyemo A. , Adoue V. , et al. .
Source: PLoS genetics, 2011 Oct; 7(10), p. e1002298.
EPub date: 2011-10-06.
PMID: 21998595
Related Citations

The landscape of recombination in African Americans.
Authors: Hinch A.G. , Tandon A. , Patterson N. , Song Y. , Rohland N. , Palmer C.D. , Chen G.K. , Wang K. , Buxbaum S.G. , Akylbekova E.L. , et al. .
Source: Nature, 2011-07-20; 476(7359), p. 170-5.
EPub date: 2011-07-20.
PMID: 21775986
Related Citations

Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21.
Authors: Haiman C.A. , Chen G.K. , Blot W.J. , Strom S.S. , Berndt S.I. , Kittles R.A. , Rybicki B.A. , Isaacs W.B. , Ingles S.A. , Stanford J.L. , et al. .
Source: Nature genetics, 2011 Jun; 43(6), p. 570-3.
EPub date: 2011-05-22.
PMID: 21602798
Related Citations

Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans.
Authors: Haiman C.A. , Chen G.K. , Blot W.J. , Strom S.S. , Berndt S.I. , Kittles R.A. , Rybicki B.A. , Isaacs W.B. , Ingles S.A. , Stanford J.L. , et al. .
Source: PLoS genetics, 2011 May; 7(5), p. e1001387.
EPub date: 2011-05-26.
PMID: 21637779
Related Citations

Validation of genome-wide prostate cancer associations in men of African descent.
Authors: Chang B.L. , Spangler E. , Gallagher S. , Haiman C.A. , Henderson B. , Isaacs W. , Benford M.L. , Kidd L.R. , Cooney K. , Strom S. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Jan; 20(1), p. 23-32.
EPub date: 2010-11-11.
PMID: 21071540
Related Citations

Relationship between plasma carotenoids and prostate cancer.
Authors: Chang S. , Erdman J.W. , Clinton S.K. , Vadiveloo M. , Strom S.S. , Yamamura Y. , Duphorne C.M. , Spitz M.R. , Amos C.I. , Contois J.H. , et al. .
Source: Nutrition and cancer, 2005; 53(2), p. 127-34.
PMID: 16573373
Related Citations

Reduced expression of hMSH2 and hMLH1 and risk of prostate cancer: a case-control study.
Authors: Strom S.S. , Spitz M.R. , Yamamura Y. , Babaian R.J. , Scardino P.T. , Wei Q. .
Source: The Prostate, 2001-06-01; 47(4), p. 269-75.
PMID: 11398174
Related Citations

Limiting the location of putative human prostate cancer tumor suppressor genes on chromosome 18q.
Authors: Yin Z. , Babaian R.J. , Troncoso P. , Strom S.S. , Spitz M.R. , Caudell J.J. , Stein J.D. , Kagan J. .
Source: Oncogene, 2001-04-26; 20(18), p. 2273-80.
PMID: 11402322
Related Citations

Leptin and prostate cancer.
Authors: Chang S. , Hursting S.D. , Contois J.H. , Strom S.S. , Yamamura Y. , Babaian R.J. , Troncoso P. , Scardino P.S. , Wheeler T.M. , Amos C.I. , et al. .
Source: The Prostate, 2001-01-01; 46(1), p. 62-7.
PMID: 11170133
Related Citations

Phytoestrogen intake and prostate cancer: a case-control study using a new database.
Authors: Strom S.S. , Yamamura Y. , Duphorne C.M. , Spitz M.R. , Babaian R.J. , Pillow P.C. , Hursting S.D. .
Source: Nutrition and cancer, 1999; 33(1), p. 20-5.
PMID: 10227039
Related Citations

Development of a database for assessing dietary phytoestrogen intake.
Authors: Pillow P.C. , Duphorne C.M. , Chang S. , Contois J.H. , Strom S.S. , Spitz M.R. , Hursting S.D. .
Source: Nutrition and cancer, 1999; 33(1), p. 3-19.
PMID: 10227038
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