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: 10350432
• 负责人: Luis Rustveld
• 金额: $ 46.43万
• 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/10350432
• 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; Clinical Research; Consumption; Cystathionine beta-Synthase; Data; Data Set; Diagnosis; Diagnostic; Diet; Diet Modification; Dietary Practices; Enzymes; Epidemiologic Factors; Epidemiology; European; Exhibits; Fishes; Food; Future; Genes; 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 Genetics; National Health and Nutrition Examination Survey; Neoplasm Metastasis; Non-Invasive Cancer 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 Factors; Vitamin B6; Work; Xenograft Model; base; 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; 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; 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.

项目摘要/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 代谢产物同型半胱氨酸与具有较高西非血统的男性显著相关 临床前列腺癌标记物前列腺特异性抗原水平升高和已确诊的患者 患有前列腺癌。我们的研究进一步揭示了维生素B6水平的显著降低和独特的饮食 在患前列腺癌风险较高的非裔美国男性中的做法。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癌转移(或扩散)到骨中的作用，这是 主要见于非裔美国人患者。 基于这些发现，在这项应用中，我们建议确定不同饮食之间的关联 非裔美国人的行为和同型半胱氨酸水平升高与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中的生物学作用。 以及非裔美国人前列腺癌的发展。我们还将评估综合水平的能力 血浆中三种代谢物：同型半胱氨酸、蛋氨酸和维生素B6，用于前列腺癌的早期检测 非裔美国人。 这项研究的影响依赖于了解饮食和饮食模式在前列腺癌发病中的作用 制定健康生活方式干预措施的风险和潜力(例如，饮食调整、维生素B6 补充等)以降低AA患者发生前列腺癌的风险。从长远来看，同型半胱氨酸和 维生素B6可作为筛查罹患前列腺癌风险较高的AA患者的标志物。