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.