Elevated homocysteine in African American Prostate Cancer: Association with Diet and Dietary practices, evaluating its biomarker potential, and characterizing its tumor promoting function

非裔美国人前列腺癌中同型半胱氨酸升高：与饮食和饮食习惯的关联，评估其生物标志物潜力，并表征其肿瘤促进功能

• 批准号: 10545052
• 负责人: Luis Rustveld
• 金额: $ 45.5万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10545052
• 关键词: Address; African American; African ancestry; Age; American; Area Under Curve; Benign; Biological; Biological Factors; Biological Markers; Biopsy; Cardiovascular Diseases; Cells; Chickens; Clinical; Consumption; Cystathionine beta-Synthase; Data; Data Set; Diagnosis; Diagnostic; Diet; Diet Modification; Dietary Practices; Disparity; Enzymes; Epidemiologic Factors; Epidemiology; European; Exhibits; Fishes; Food; Future; Genes; Genetic; Glean; Growth and Development function; High temperature of physical object; Homocysteine; In Vitro; Incidence; Intake; Intervention; Knowledge; LNCaP; Link; Malignant neoplasm of prostate; Mass Spectrum Analysis; Meat; Medicine; Metabolic; Metabolism; Metastatic Neoplasm to the Bone; Methionine; Methods; Modeling; Molecular; National Health and Nutrition Examination Survey; Neoplasm Metastasis; Non-Invasive Detection; Odds Ratio; Organ; PSA level; Pathologic; Pathway interactions; Patients; Plasma; Population Study; Processed Meats; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Neoplasms; Publishing; Race; Research; Risk; Role; Screening for Prostate Cancer; Side; Supplementation; Tenascin; Testing; Therapeutic; Time; Tissues; Training; Transcript; Transforming Growth Factor beta; Tumor Promotion; Vitamin B6; Work; Xenograft Model; beef; biomarker panel; bone; cancer biomarkers; cancer health disparity; case control; cell growth; clinically significant; cofactor; college; cooking; early detection biomarkers; epidemiologic data; follow-up; gain of function; health disparity; healthy lifestyle; high risk; high risk men; in vivo; lifestyle intervention; loss of function; men; metabolome; mortality; population based; prognostic; prostate biopsy; prostate cancer cell; prostate cancer progression; prostate cancer risk; racial difference; risk mitigation; saturated fat; socioeconomics; tumor; tumor progression

Project Summary/Abstract Our research plan's long-term objective is to reduce the disproportionate effects of prostate cancer on African American men. In our published and yet to be published studies, we have found that increased levels of a metabolite homocysteine were significantly associated with men with higher West African ancestry who have elevated levels of the clinical prostate cancer marker prostate-specific antigen and who have been diagnosed with prostate cancer. Our work further reveals significantly reduced levels of vitamin B6 and unique dietary practices in African American men who are at high risk of developing prostate cancer. Also, we show a possible role for elevated homocysteine in promoting metastasis (or spread) of the prostate tumors to the bone, which is predominantly seen in African American patients. Based on these findings, in this application, we propose determining the association between different dietary practices and elevated levels of homocysteine and the likelihood of having prostate cancer in African American men. In addition, we propose to determine the biological role of elevated homocysteine in promoting the growth and development of African American prostate cancer. We will also evaluate the ability of combined levels of three metabolites: homocysteine, methionine, and vitamin B6, in plasma, to detect prostate cancer early in African American men. This study's impact relies on understanding the role of diet and dietary patterns in contributing to prostate cancer risk and the potential to develop healthy lifestyle interventions (e.g., dietary modification, vitamin B6 supplementation, etc.) to mitigate the risk of developing PCa in AA men. In the longer term, homocysteine and vitamin B6 could be set as markers to screen AA men at higher risk of developing PCa.

项目概要/摘要 我们研究计划的长期目标是减少前列腺癌对非洲人的不成比例的影响 美国男人。在我们已发表和尚未发表的研究中，我们发现 代谢物同型半胱氨酸与具有较高西非血统的男性显着相关。 临床前列腺癌标志物前列腺特异性抗原水平升高以及已被诊断的人群 患有前列腺癌。我们的工作进一步揭示了维生素 B6 水平显着降低和独特的饮食 在患前列腺癌的高风险非裔美国男性中进行实践。此外，我们还展示了一种可能的 同型半胱氨酸升高在促进前列腺肿瘤向骨转移（或扩散）中的作用，这是 主要见于非裔美国患者。 基于这些发现，在本申请中，我们建议确定不同饮食之间的关联 非裔美国人的实践和同型半胱氨酸水平升高以及患前列腺癌的可能性 男人。此外，我们建议确定升高的同型半胱氨酸在促进生长方面的生物学作用 和非洲裔美国人前列腺癌的发展。我们还将评估综合水平的能力 血浆中的三种代谢物：同型半胱氨酸、蛋氨酸和维生素 B6，用于早期检测前列腺癌 非裔美国男性。 这项研究的影响依赖于了解饮食和饮食模式在导致前列腺癌中的作用 风险和开发健康生活方式干预措施的潜力（例如饮食调整、维生素 B6 补充剂等）以降低 AA 男性患 PCa 的风险。从长远来看，同型半胱氨酸和 维生素 B6 可以作为筛查 AA 男性患 PCa 风险较高的标志物。