For all three models AA remains the significant factor for methylation. The methylation profile for all but one PTPRD gene was similar in both MSI-H and non-MSI-H tumors, confirming an alreadyestablished dissociation between the CpG island methylator phenotype and the microsatellite instability phenotype in colon cancer tumors. The PTPRD gene encodes a protein that is a member of the protein tyrosine phosphatase family, signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This finding is also reinforced by the fact that another gene involved in metastasis, ICAM5, is highly methylated in AA when compared to Iranians. ICAM5 encodes a type I transmembrane glycoprotein that is a member of the intercellular adhesion molecule family. High methylation level of ICAM5 decreases the cell-to-cell adhesion in the corresponding tumor cells, increasing their invasive potential. This finding is consistent with the GPNMB results leading to cumulative effects that increase the invasiveness and metastatic potential. Unlike GPNMB and ICAM5, CHD-5 seems to be involved in early tumorigenic processes at the chromatin remodeling level and controls events, such as proliferation, apoptosis, and senescence, via the p19 / p53 pathway. The methylation level of this gene in AA might reflect the high level of incidence of colon cancer in AA. Indeed, chromatin modification affects the expression profiles of many genes at once and impacts the quick progression of the tumor. Our recent publications have shown that AA colon Hederagenin tumors display an aberrant global histone acetylation and HDAC2 expression. The hypermethylation of those genes that showed similarities between the two populations may be an early silencing marker for CRC initiation. Based on the Isoliquiritin obtained results and known characteristics of AA CRC, the CAN genes methylation results support the highly methylated CHD5 and ICAM5 in the AA tumors, pointing to a prominent role of CHD5 and ICAM5. There was a consistent result between CHD5 methylation and lack of CHD5 protein expression using IHC.