Here, we report that hypermethylation of the anti-inflammatory transcription factors NELL1, GDF1, ARHGEF4, and ITGA4 and multiple miRNAs including miR-9-3p and miR-124-3p may be factors driving the disparity observed in incidence of CRC between racial and ethnic groups. This evidence concerns the gene ARHGEF4 and colorectal carcinoma.