Prostate Microenvironmental & Prostate Cancer Progression

前列腺微环境

• 批准号: 7048051
• 负责人: JUNE ML CHAN
• 金额: $ 51.02万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048051
• 关键词: antioxidants; carotenoids; clinical research; genes; genotype; neoplasm /cancer; prostate; prostate neoplasms

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的进展 - 染色体损伤和基因组不稳定性是癌变的标志，微量营养素和遗传学相互作用以保护基因组免受这一有害过程。我们小组和其他人的最新证据表明，几种抗氧化剂营养可能可以防止前列腺癌的发展，并且与DNA修复有关的遗传变异和抗氧化剂代谢可能会改变诊断前抗氧化剂对前列腺癌风险的影响。 Through the following 3 Specific Aims, we will expand on these findings and investigate whether circulating post-diagnostic antioxidants (i.e. l​​ycopene, total carotenoids, alpha- & gamma- tocopherol, and selenium) and genotypes (i.e. MnSOD, GPX1, GSTM1, GSTT1, XRCC1, OGG1) are associated with: (Aim 1) prostate cancer临床表型：（目标2）前列腺肿瘤基因组不稳定性：（AIM 3）复发/进展的风险。诊断时的格里森评分（活检）将反映临床表型；全球肿瘤拷贝数的畸变将表明肿瘤胶状不稳定性。我们将评估一项现有研究的1000名男性被诊断出患有局部/区域前列腺癌，在治疗之前捐赠血液和组织以进行研究，并同意随访。我们假设较低的循环番茄红素，总类胡萝卜素，α和γ-生育酚以及硒和特定基因变异将与Gleason评分的提高，肿瘤基因组不稳定性以及复发/进展的风险有关。我们还假设这些循环抗氧化剂和遗传变异将相互作用以影响侵略性和疾病。该项目的目的是确定癌症开始后的抗氧化剂营养是否会影响肿瘤的攻击性和进展，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）在现有研究中建立效率，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的优质资源。这项研究可能会通过制定针对癌症患者的新营养准则，或启动抗氧化剂干预措施的佐剂或新辅助随机临床试验的新营养准则，从而改善公共卫生，这是针对具有特定基因型种群的。