Prostate Microenvironmental & Prostate Cancer Progression

前列腺微环境

基本信息

批准号：
7666279
负责人：
JUNE ML CHAN
金额：
$ 25.96万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7666279
关键词：
Address Adjuvant Affect Antioxidants Antioxidants Nutrition Base Excision Repairs Biopsy Blood Blood specimen California Cancer Center Cancer Patient Candidate Disease Gene Carotenoids Clinic Clinical Clinical Course of Disease Clinical Research Collaborations Comprehensive Cancer Center Consent Consumption DNA Repair Dana-Farber Cancer Institute Data Development Diagnosis Diagnostic Discipline Disease Food Future GSTM1 gene GSTT1 gene Genes Genetic Genetic Variation Genome Genome Stability Genomic Instability Genomics Genotype Germ Lines Gleason Grade for Prostate Cancer Goals Haplotypes Intervention Intervention Trial Knowledge Lead Life Malignant neoplasm of prostate Measures Metabolism Micronutrients Neoadjuvant Therapy Newly Diagnosed Nutrient Nutritional OGG1 gene Outcome Persons Physiological Population Primary Prevention Process Prostate Prostatic Neoplasms Public Health Randomized Clinical Trials Recording of previous events Recurrence Research Research Personnel Resources Risk Risk Factors San Francisco Secondary Prevention Selenium Serum Study of serum Systems Biology Tissues Tumor Markers Universities Urologic Oncology Variant XRCC1 gene cancer genetics cancer initiation cancer recurrence cancer risk carcinogenesis clinical phenotype follow-up gamma-Tocopherol genetic epidemiology genetic variant improved innovation lycopene men modifiable risk novel nutrition nutritional guideline public health relevance repaired tumor tumor progression

项目摘要

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.

描述（由申请人提供）：前列腺微环境和前列腺癌进展 - 染色体损伤和基因组不稳定性是致癌的标志，微量营养素和遗传学相互作用以保护基因组免受这种有害过程的影响。我们小组和其他人的最新证据表明，几种抗氧化营养素可以预防前列腺癌的发展，而与 DNA 修复和抗氧化代谢有关的遗传变异可能会改变诊断前抗氧化状态对前列腺癌风险的影响。通过以下 3 个具体目标，我们将扩展这些发现，并研究循环诊断后抗氧化剂（即番茄红素、总类胡萝卜素、α-和γ-生育酚和硒）和基因型（即 MnSOD、GPX1、GSTM1、GSTT1、 XRCC1、OGG1) 与：（目标 1）前列腺癌临床表型相关：（目标 2）前列腺肿瘤基因组不稳定性：和（目标 3）复发/进展风险。诊断（活检）时的格里森评分将反映临床表型；整体肿瘤拷贝数畸变将表明肿瘤微生物的不稳定性。我们将对现有研究中的 1000 名男性进行评估，这些男性被诊断患有局部/区域性前列腺癌，在治疗前出于研究目的捐献血液和组织，并同意进行随访。我们假设较低的循环番茄红素、总类胡萝卜素、α-和γ-生育酚、硒和特定基因变异将与格里森评分增加、肿瘤基因组不稳定性和复发/进展风险相关。我们还假设这些循环抗氧化剂和遗传变异会相互作用，影响疾病的侵袭性和病程。该项目的目标是确定癌症发生后的抗氧化营养是否会影响肿瘤的侵袭性和进展，以及这是否取决于基因型。这项研究的优势包括 1) 科学新颖性和重要性，2) 现有研究的效率，3) 临床和公共卫生相关性，4) 多学科合作研究团队，以及 5) UGSF 和 DFCI 的优秀资源。这项研究可能会通过为癌症患者制定新的营养指南，或启动针对特定基因型人群的抗氧化干预的辅助或新辅助随机临床试验来改善公众健康。