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Grant Details

Grant Number: 5R01CA106947-04 Interpret this number
Primary Investigator: Chan, June
Organization: University Of California, San Francisco
Project Title: Prostate Microenvironmental & Prostate Cancer Progression
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): Prostate microenvironment and prostate cancer progression - Chromosomal damage and genomic instability are hallmarks of carcinogenesis, and micronutrients and genetics interact to protect the genome against this deleterious process. Recent evidence from our group and others suggests that several antioxidant nutrients may protect against the development of prostate cancer, and genetic variants involved with DNA repair and antioxidant metabolism may modify the influence of pre-diagnostic antioxidant status on prostate cancer risk. Through the following 3 Specific Aims, we will expand on these findings and investigate whether circulating post-diagnostic antioxidants (i.e. lycopene, total carotenoids, alpha- & gamma- tocopherol, and selenium) and genotypes (i.e. MnSOD, GPX1, GSTM1, GSTT1, XRCC1, OGG1) are associated with: (Aim 1) prostate cancer clinical phenotype: (Aim 2) prostate tumor genomic instability: and (Aim 3) risk of recurrence/ progression. Gleason score at diagnosis (biopsy) will reflect clinical phenotype; and global tumor copy number aberrations will indicate tumor gerbmic instability. We will evaluate 1000 men from an existing study who were diagnosed with incident localized/regional prostate cancer, donated blood and tissue for research purposes prior to treatment, and consented to follow-up. We hypothesize that lower circulating lycopene, total carotenoids, alpha- & gamma-tocopherol, and selenium and specific gene variants will be associated with increased Gleason score, tumor genomic instability, and risk of recurrence/progression. We also hypothesize that these circulating antioxidants and genetic variants will interact to affect the aggressiveness and course of disease. The goal of this project is to determine whether antioxidant nutrition after cancer initiation influences tumor aggressiveness and progression, and whether this depends on genotype. Strengths of this study include the 1) scientific novelty and importance, 2) efficiency of building on existing studies, 3) clinical and public health relevance, 4) multi-disciplinary collaborative research team, and 5) excellent resources of UGSF and DFCI. This study may lead to improved public health through the development of new nutritional guidelines for cancer patients, or the initiation of adjuvant or neoadjuvant randomized clinical trials of antioxidant interventions, focused on populations with specific genotypes.

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Publications

Plasma antioxidants, genetic variation in SOD2, CAT, GPX1, GPX4, and prostate cancer survival.
Authors: Van Blarigan EL, Ma J, Kenfield SA, Stampfer MJ, Sesso HD, Giovannucci EL, Witte JS, Erdman JW Jr, Chan JM, Penney KL
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jun;23(6), p. 1037-46.
EPub date: 2014 Apr 7.
PMID: 24711484
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What should we tell prostate cancer patients about (secondary) prevention?
Authors: Chan JM, Van Blarigan EL, Kenfield SA
Source: Curr Opin Urol, 2014 May;24(3), p. 318-23.
PMID: 24625429
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Aspirin use after a prostate cancer diagnosis and cancer survival in a prospective cohort.
Authors: Dhillon PK, Kenfield SA, Stampfer MJ, Giovannucci EL, Chan JM
Source: Cancer Prev Res (Phila), 2012 Oct;5(10), p. 1223-8.
EPub date: 2012 Sep 7.
PMID: 22961777
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Single-nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer.
Authors: Abe M, Xie W, Regan MM, King IB, Stampfer MJ, Kantoff PW, Oh WK, Chan JM
Source: BJU Int, 2011 Jan;107(1), p. 126-34.
PMID: 20477822
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Plasma selenium, manganese superoxide dismutase, and intermediate- or high-risk prostate cancer.
Authors: Chan JM, Oh WK, Xie W, Regan MM, Stampfer MJ, King IB, Abe M, Kantoff PW
Source: J Clin Oncol, 2009 Aug 1;27(22), p. 3577-83.
EPub date: 2009 Jun 15.
PMID: 19528373
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