The major findings of our investigation are that: (i) obesity and CC reduce circulating and gene expression levels of MAGP-1; (ii) inflammation-related factors and hypoxia regulate MFAP2 mRNA levels in HT-29 colon cancer cells; (iii) MAGP-1 modulates the expression of ECM-related and tumorigenesis genes in HT-29 cells and (iv) the ACM obtained from patients with obesity downregulates the gene expression levels of MFAP2 in HT-29 cells. Here, MFAP2 is linked to colonic neoplasm.