|Grant Number:||5R01CA106947-04 Interpret this number|
|Primary Investigator:||Chan, June|
|Organization:||University Of California, San Francisco|
|Project Title:||Prostate Microenvironmental & Prostate Cancer Progression|
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.
Selenium- Or Vitamin E-related Gene Variants, Interaction With Supplementation, And Risk Of High-grade Prostate Cancer In Select
Authors: Chan J.M. , Darke A.K. , Penney K.L. , Tangen C.M. , Goodman P.J. , Lee G.S. , Sun T. , Peisch S. , Tinianow A.M. , Rae J.M. , 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 Jul; 25(7), p. 1050-8.
Association Of Genetic Variations Of Selenoprotein Genes, Plasma Selenium Levels, And Prostate Cancer Aggressiveness At Diagnosis
Authors: Xie W. , Yang M. , Chan J. , Sun T. , Mucci L.A. , Penney K.L. , Lee G.S. , Kantoff P.W. .
Source: The Prostate, 2016 May; 76(7), p. 691-9.
Associations Between Circulating Carotenoids, Genomic Instability And The Risk Of High-grade Prostate Cancer
Authors: Nordström T. , Van Blarigan E.L. , Ngo V. , Roy R. , Weinberg V. , Song X. , Simko J. , Carroll P.R. , Chan J.M. , Paris P.L. .
Source: The Prostate, 2016 Mar; 76(4), p. 339-48.
Germline Variation In Superoxide Dismutase-2 (sod2) And Survival Outcomes After Radiation Therapy For Prostate Cancer: Results Of A Test And Validation Set Analysis
Authors: Margalit D.N. , Jordahl K.M. , Werner L. , Wang X. , Gwo-Shu Lee M. , Penney K.L. , Batista J.L. , Martin N.E. , Chan J.M. , Kantoff P.W. , et al. .
Source: Clinical Genitourinary Cancer, 2015 Aug; 13(4), p. 370-377.e1.
Selenoprotein And Antioxidant Genes And The Risk Of High-grade Prostate Cancer And Prostate Cancer Recurrence
Authors: Gerstenberger J.P. , Bauer S.R. , Van Blarigan E.L. , Sosa E. , Song X. , Witte J.S. , Carroll P.R. , Chan J.M. .
Source: The Prostate, 2015 Jan; 75(1), p. 60-9.
Plasma Antioxidants, Genetic Variation In Sod2, Cat, Gpx1, Gpx4, And Prostate Cancer Survival
Authors: Van Blarigan E.L. , Ma J. , Kenfield S.A. , Stampfer M.J. , Sesso H.D. , Giovannucci E.L. , Witte J.S. , Erdman J.W. , Chan J.M. , Penney K.L. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2014 Jun; 23(6), p. 1037-46.
What Should We Tell Prostate Cancer Patients About (secondary) Prevention?
Authors: Chan J.M. , Van Blarigan E.L. , Kenfield S.A. .
Source: Current Opinion In Urology, 2014 May; 24(3), p. 318-23.
Aspirin Use After A Prostate Cancer Diagnosis And Cancer Survival In A Prospective Cohort
Authors: Dhillon P.K. , Kenfield S.A. , Stampfer M.J. , Giovannucci E.L. , Chan J.M. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2012 Oct; 5(10), p. 1223-8.
Single-nucleotide Polymorphisms Within The Antioxidant Defence System And Associations With Aggressive Prostate Cancer
Authors: Abe M. , Xie W. , Regan M.M. , King I.B. , Stampfer M.J. , Kantoff P.W. , Oh W.K. , Chan J.M. .
Source: Bju International, 2011 Jan; 107(1), p. 126-34.
Plasma Selenium, Manganese Superoxide Dismutase, And Intermediate- Or High-risk Prostate Cancer
Authors: Chan J.M. , Oh W.K. , Xie W. , Regan M.M. , Stampfer M.J. , King I.B. , Abe M. , Kantoff P.W. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2009-08-01 00:00:00.0; 27(22), p. 3577-83.