The current analyses indicated that the three RUNX3, RASSF1A and Reprimo genes promoter methylation had better diagnostic capacity (RUNX3: sensitivity = 63.2% and specificity = 97.5%, RASSF1A: sensitivity = 61.5% and specificity = 96.3%, Reprimo: sensitivity = 82.0% and specificity = 89.0%), which suggested that the three tumor-related genes could become potential noninvasive biomarkers using blood samples for the early detection of GC, particularly Reprimo promoter methylation. This evidence concerns the gene RPRM and neoplasm.