Prostate cancer is the most common cancer among men. The purpose of this quantitative, meta-analysis study was to examine one-carbon metabolism gene polymorphisms in a group of genes to determine their association with prostate cancer risk. The genetic epidemiology theory provided the framework for the study. The data collected were from published articles. From over 2,800 individual studies, 20 articles were retained for results and data abstraction, following the title, abstract screen, and full text screening in the second phase. The data were analyzed by a meta-analysis statistical method, combining the results from selected studies to estimate the overall association. According to study results by the adjusted p-values of fixed model, there was a significant association between decreased risk of prostate cancer and the variant of Allele T, Genotype TT, and the recessive model of C667T polymorphism. In the random model, the adjusted p-values show a significant association between decreased risk of prostate cancer, the variant of Genotype TT, and recessive model. There was an increased risk of prostate cancer in A1298C polymorphism by adjusted p-value on the variant of Genotype AC, in the fixed model. This study leads to positive social change by providing information on an optimization surveillance strategy to ensure valid screening test for prostate disease reporting. Future studies with a greater number of samples are needed, including gene-gene and gene-environment interaction to verify study results.