Significant association of MCP1 rs1024611 and CCR2 rs1799864 polymorphisms with colorectal cancer and liver metastases susceptibility and aggressiveness: A case-control study

• Published in: Cytokine (Philadelphia, Pa.) Vol. 167; p. 156193
• Main Authors: Boughriba, Rahma, Sahraoui, Ghada, Chaar, Ines, Weslati, Marwa, Ayed, Khouloud, Ounissi, Donia, Hazgui, Mariem, Bouraoui, Saadia, Gati, Asma
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2023
• Subjects: Case-Control Studies; CCR2; Chemokine CCL2 - genetics; Chemotherapy; Colorectal cancer; Colorectal liver metastasis; Colorectal Neoplasms - genetics; Humans; Liver Neoplasms - genetics; MCP1; Overall survival; Polymorphism; Polymorphism, Single Nucleotide - genetics; Receptors, CCR2 - genetics; Retrospective Studies; Risk Factors; Treatment approaches; Tumor Microenvironment; Chemotherapy; MCP1; Treatment approaches; Colorectal cancer; Colorectal liver metastasis; Overall survival; CCR2; Polymorphism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2023.156193

•MCP1 rs1024611 and CCR2 rs1779864 were associated with increased CRC and CRLM risk, elevated CEA serum levels, and poor prognostic features.•Poor survival rate was noted among MCP1 rs1024611 mutated genotype carriers.•Neoadjuvant treatment based on radio- or radiochemotherapy showed survival rate improvement among MCP1 and CCR2 wild-type genotypes carriers.•FOLFIRI chemotherapy was associated with decreased CRC survival rate among MCP1 and CCR2 mutated genotypes carriers. The MCP-1/CCR2 axis is one of the major chemokine signaling pathways that play a crucial role in the tumor microenvironment and has been involved in triggering various tumor progression mechanisms, such as increasing the immunosuppressive cells recruitment and promoting tumor cell proliferation and invasiveness. The current study investigated the association of MCP1 (rs1024611) and CCR2 (rs1799864) genes variants with the risk as well as prognosis of colorectal cancer (CRC) and colorectal liver metastases (CRLM). A retrospective cohort study involved 408 patients (284 CRC and 124 CRLM), and 284 healthy control was conducted. Genotyping of selected polymorphisms was performed by PCR-RFLP assays and confirmed by microchip and capillary electrophoresis. The results highlighted a positive association between MCP1 rs1024611 (non-AA) and CCR2 rs1799864 (GA) genotypes with increased CRC and CRLM risk. Correlation between SNPs and clinicopathological characteristics revealed a positive association between MCP1 rs1024611 and CCR2 rs1799864 (dominant model) and CRC poor prognosis features. Kaplan-Meier survival analysis revealed a significant association between MCP1 rs1024611 non-AA carriers and decreased survival rate. Neoadjuvant treatment showed an improvement in CRC and CRLM survival rates among carriers of MCP1 and CCR2 wild-type genotype. FOLFIRI chemotherapy exhibits reduced survival rates for patients who carried mutated genotypes of MCP1 and CCR2 polymorphisms. Considering our results, we suggest That both MCP1 and CCR2 polymorphisms may constitute independent factors for CRC and CRLM occurrence and can be helpful targets for an efficient therapeutic approach.