Association of CCR5Δ32 Deletion and Human Cytomegalovirus Infection With Colorectal Cancer in Tunisia

Abstract

Background and objectives: Human cytomegalovirus (HCMV) and genetic polymorphisms of the chemokine receptor 5 have been suggested as factors associated with the progression of colorectal cancer (CRC). The aim of the study was to evaluate the associations of both CCR5Δ32 genetic deletion and/or HCMV virus infection with CRC in Tunisia. Materials and methods: The association between HCMV and CRC was validated by Nested PCR technology performed for HCMV and HCMV-specific serum IgG and IgM antibodies were investigated by enzyme-linked immunosorbent assay. Experiments were carried out on 40 tumor and 35 peri-tumor tissues, 100 blood from CRC patients and on 140 blood samples from healthy subjects and finaly serum samples of 80 patients with CRC and 100 healthy individuals. A conventional PCR has been optimized for the detection of CCR5Δ32 in100 CRC patients and 100 healthy subjects. Results: Our results show that HCMV is significantly active in 93% of patients compared to 60% in controls (p < 0.0001, OR = 8.85, 95% CI: 3.82 -20.50). Compared to the healthy controls, the titers of IgG and IgM antiCMV antibodies in CRC patients were significantly higher than in healthy subjects (p value < 0,0001 for IgG and IgM). Statistical analysis revealed a lack of association between CCR5Δ32 mutation and colorectal cancer (p = 0.788, OR = 1.265, 95% CI: 0.228-7.011). Conclusion: our data confirmed that the HCMV infection was related to the development of CRC and that CRC cells may be infected more favorably by HCMV. Given the importance of the CCR5 in inflammation and therefore CRC progression, further studies still needed to evaluate CCR5 role as a potential candidate gene for CRC susceptibility under other polymorphisms.

Network Pharmacology-Integrated Molecular Docking Reveals the Expected Anticancer Mechanism of Picrorhizae Rhizoma Extract

“…The PI3K-Akt signaling pathway promotes liver cancer cell proliferation and metastasis [60]. In human cytomegalovirus infection, there is association of CCR5Δ32 deletion and human cytomegalovirus infection with colorectal cancer in Tunisia [61]. Kaposi sarcoma-associated herpesvirus infection regulates proliferation of glioma stem-like cells [62], relieves the Warburg effect through p53 activation, thereby inhibiting breast cancer cell growth [63], inhibits renal cancer cell growth by regulating the p53 signaling pathway [48], suppresses lung cancer growth by activating the p53 signaling pathway [64], promotes cholangiocarcinoma cell proliferation, migration, and invasion by decreasing p53 expression [65], and promotes pancreatic cancer growth and metastasis through the p53 transcriptional pathway [66].…”

Detection of Human cytomegalovirus UL55 Gene and IE/E Protein Expression in Colorectal Cancer Patients in Egypt

“…On the other hand, recently Chelbi et al . showed no difference of UL55 gene detection in tumor versus peritumor tissues [ 25 ]. Also, earlier studies found no relation between HCMV and CRC [ 26 – 28 ].…”