Grant Number:	5R01CA072036-03 Interpret this number
Primary Investigator:	Giovannucci, Edward
Organization:	Harvard University (Medical School)
Project Title:	Nutritional and Hormonal Biomarkers in Prostate Cancer
Fiscal Year:	1998

DESCRIPTION: (Adapted from the Applicant's Abstract): Prostate cancer is the most frequently diagnosed malignancy and the second most common cause of cancer death among men in the US. Our general goals are two-fold, firstly to evaluate the strongest current hypotheses regarding the etiology of prostate cancer, and secondly to complete the establishment of a large, unique database consisting of repeated dietary assessments over several decades, archived blood specimens, and archived tumor tissue for immunohistochemistry, in-situ hybridization and DNA sequencing. This resource will allow for the rapid examination of future hypotheses as they emerge. In this proposal, we focus on interrelationships between dietary factors and hormonal levels, as well as genetic susceptibility factors. Utilizing archived blood samples collected in 1993-944 from 16,300 men in the ongoing Health Professionals Follow-Up Study, we will conduct a matched, nested case-control study based on 531 new cases projected from 1993 to 2000 to evaluate several hypotheses, all of which have substantial preliminary support. Firstly, we will examine whether an association between dietary fat and prostate cancer risk is mediated through specific types of fatty acids in red blood cell phospholipids, specifically, high levels of saturated fats, a-linolenic, and trans fatty acids and low levels of long-chain omega-3 fatty acids. We will also examine whether high fat, energy and protein intake increases risk of prostate cancer through hormonal mechanisms, involving both steroid hormones and insulin-like growth factor-1. Secondly, we will examine whether high intake of heterocyclic amines formed from the prolonged cooking of meat at high temperatures, as well as smoking history, are associated with prostate tumors possessing mutations in p53. Thirdly, we will evaluate whether increased plasma levels of specific carotenoids, particularly lycopene and a-tocopherol reduce risk of prostate cancer. Finally, we will examine the hormonal hypothesis of prostate carcinogenesis in substantial detail by assessing plasma testosterone, dihydrotestosterone, estradiol, and serum hormone binding globulin, as well as CAG repeats in the androgen receptor gene (possibly correlated with elevated transactivation of the androgen receptor), and TA repeats of the 5-a-reductase enzyme (which may influence mRNA stability and subsequently cellular levels of this enzyme). These studies will enhance our understanding of prostate carcinogenesis and provide a scientific foundation for future preventive efforts.




Current or recent smoking is associated with more variable telomere length in prostate stromal cells and prostate cancer cells.
Authors: Joshu C.E. , Peskoe S.B. , Heaphy C.M. , Kenfield S.A. , Mucci L.A. , Giovannucci E.L. , Stampfer M.J. , Yoon G. , Lee T.K. , Hicks J.L. , et al. .
Source: The Prostate, 2017-11-22 00:00:00.0; , .
EPub date: 2017-11-22 00:00:00.0.
PMID: 29164645
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Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies.
Authors: Key T.J. , Appleby P.N. , Travis R.C. , Albanes D. , Alberg A.J. , Barricarte A. , Black A. , Boeing H. , Bueno-de-Mesquita H.B. , Chan J.M. , et al. .
Source: The American Journal Of Clinical Nutrition, 2015 Nov; 102(5), p. 1142-57.
PMID: 26447150
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Prediagnostic Obesity and Physical Inactivity Are Associated with Shorter Telomere Length in Prostate Stromal Cells.
Authors: Joshu C.E. , Peskoe S.B. , Heaphy C.M. , Kenfield S.A. , Van Blarigan E.L. , Mucci L.A. , Giovannucci E.L. , Stampfer M.J. , Yoon G. , Lee T.K. , et al. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2015 Aug; 8(8), p. 737-42.
PMID: 25990087
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Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death.
Authors: Heaphy C.M. , Yoon G.S. , Peskoe S.B. , Joshu C.E. , Lee T.K. , Giovannucci E. , Mucci L.A. , Kenfield S.A. , Stampfer M.J. , Hicks J.L. , et al. .
Source: Cancer Discovery, 2013 Oct; 3(10), p. 1130-41.
PMID: 23779129
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Association between plasma cholesterol and prostate cancer in the PSA era.
Authors: Platz E.A. , Clinton S.K. , Giovannucci E. .
Source: International Journal Of Cancer, 2008-10-01 00:00:00.0; 123(7), p. 1693-8.
PMID: 18646186
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Validation of a food frequency questionnaire measurement of selected nutrients using biological markers in African-American men.
Authors: Holmes M.D. , Powell I.J. , Campos H. , Stampfer M.J. , Giovannucci E.L. , Willett W.C. .
Source: European Journal Of Clinical Nutrition, 2007 Nov; 61(11), p. 1328-36.
PMID: 17299490
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Dietary patterns and risk of prostate cancer in U.S. men.
Authors: Wu K. , Hu F.B. , Willett W.C. , Giovannucci E. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2006 Jan; 15(1), p. 167-71.
PMID: 16434606
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Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era.
Authors: Platz E.A. , Leitzmann M.F. , Rifai N. , Kantoff P.W. , Chen Y.C. , Stampfer M.J. , Willett W.C. , Giovannucci E. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2005 May; 14(5), p. 1262-9.
PMID: 15894683
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Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of prostate cancer in the PSA era.
Authors: Platz E.A. , Pollak M.N. , Leitzmann M.F. , Stampfer M.J. , Willett W.C. , Giovannucci E. .
Source: Cancer Causes & Control : Ccc, 2005 Apr; 16(3), p. 255-62.
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Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer.
Authors: Platz E.A. , Leitzmann M.F. , Hollis B.W. , Willett W.C. , Giovannucci E. .
Source: Cancer Causes & Control : Ccc, 2004 Apr; 15(3), p. 255-65.
PMID: 15090720
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Plasma and dietary carotenoids, and the risk of prostate cancer: a nested case-control study.
Authors: Wu K. , Erdman J.W. , Schwartz S.J. , Platz E.A. , Leitzmann M. , Clinton S.K. , DeGroff V. , Willett W.C. , Giovannucci E. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2004 Feb; 13(2), p. 260-9.
PMID: 14973107
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Variations in plasma lycopene and specific isomers over time in a cohort of U.S. men.
Authors: Wu K. , Schwartz S.J. , Platz E.A. , Clinton S.K. , Erdman J.W. , Ferruzzi M.G. , Willett W.C. , Giovannucci E.L. .
Source: The Journal Of Nutrition, 2003 Jun; 133(6), p. 1930-6.
PMID: 12771341
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Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men.
Authors: Giovannucci E. , Pollak M. , Liu Y. , Platz E.A. , Majeed N. , Rimm E.B. , Willett W.C. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2003 Feb; 12(2), p. 84-9.
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Racial variation in prostate cancer incidence and in hormonal system markers among male health professionals.
Authors: Platz E.A. , Rimm E.B. , Willett W.C. , Kantoff P.W. , Giovannucci E. .
Source: Journal Of The National Cancer Institute, 2000-12-20 00:00:00.0; 92(24), p. 2009-17.
PMID: 11121463
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The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer.
Authors: Febbo P.G. , Kantoff P.W. , Platz E.A. , Casey D. , Batter S. , Giovannucci E. , Hennekens C.H. , Stampfer M.J. .
Source: Cancer Research, 1999-12-01 00:00:00.0; 59(23), p. 5878-81.
PMID: 10606227
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Racial variation in insulin-like growth factor-1 and binding protein-3 concentrations in middle-aged men.
Authors: Platz E.A. , Pollak M.N. , Rimm E.B. , Majeed N. , Tao Y. , Willett W.C. , Giovannucci E. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 1999 Dec; 8(12), p. 1107-10.
PMID: 10613344
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Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature.
Authors: Giovannucci E. .
Source: Journal Of The National Cancer Institute, 1999-02-17 00:00:00.0; 91(4), p. 317-31.
PMID: 10050865
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The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia.
Authors: Giovannucci E. , Platz E.A. , Stampfer M.J. , Chan A. , Krithivas K. , Kawachi I. , Willett W.C. , Kantoff P.W. .
Source: Urology, 1999 Jan; 53(1), p. 121-5.
PMID: 9886600
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Debrisoquine hydroxylase (CYP2D6) and prostate cancer.
Authors: Febbo P.G. , Kantoff P.W. , Giovannucci E. , Brown M. , Chang G. , Hennekens C.H. , Stampfer M. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 1998 Dec; 7(12), p. 1075-8.
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