The role of CCR5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population

Authors

  • Marwa Weslati 1. Laboratory of Molecular Genetics Immunology and Biotechnology (LR99ES12), Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia; 2. Colorectal Cancer Research Laboratory UR12SP14, Mongi Slim Hospital, La Marsa, Tunisia https://orcid.org/0000-0001-5641-8754
  • Rahma Boughriba Laboratory of Genetics Immunology and Human Pathology (LR05ES05), Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia https://orcid.org/0000-0002-6824-8307
  • Donia Ounissi Laboratory of Neurophysiology, Cellular Physiopathology and Biomolecule Valorization (LR18ES03), Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia https://orcid.org/0000-0003-4585-271X
  • Meriam Hazgui Laboratory of Mycology, Pathologies and Biomarkers (LR16ES05), Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia https://orcid.org/0000-0003-2195-6469
  • Sonia Marghali Laboratory of Molecular Genetics Immunology and Biotechnology (LR99ES12), Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia https://orcid.org/0000-0002-3090-1454

DOI:

https://doi.org/10.2298/ABS210817044W

Keywords:

CCR5Δ32, colorectal cancer, liver metastasis, Tunisian cohort, chemokines

Abstract

Paper description:

  • Colorectal cancer results from the accumulation of genetic and epigenetic alterations and complex interactions between tumor cells and the tumor microenvironment. Understanding genetic differences in populations helps develop specific and more effective treatments.
  • Research targeting C-C chemokine receptor type 5 (CCR5) (rs333) in both colorectal cancer and colorectal cancer liver metastases are inconclusive. We investigated the impact of this mutation in different stages.
  • CCR5Δ32 reduced colorectal cancer risk; all metastases had wild type CCR5.
  • Having a dysfunctional/repressed CCR5 receptor is unfavorable to colorectal cancer and colorectal cancer liver metastases development, CCR5Δ32 might protect against CRC development and dissemination.

Abstract: Chemokines and their receptors are involved in cancer initiation and progression, including colorectal cancer (CRC) and liver metastasis formation. Our aim was to elucidate C-C chemokine receptor type 5 (CCR5) gene polymorphism (CCR5Δ32) impact on CRC and colorectal cancer liver metastases (CRLM) occurrence risk. We analyzed the CCR5 gene mutational status in 108 primary CRC cases, 35 CRLM and 248 healthy individuals, and evaluated CCR5 expression in healthy tissue and tumors. Rare allele “Δ32” was more frequent in controls (7.2% vs 2.8% in CRC). All 35 metastases had wild-type CCR5. Our analysis showed that CCR5 wild type has a significant risk of 2.73-fold (95% CI=1.22-7.31) to cause CRC while Δ32 reduced the risks 0.36-fold (95% CI=0.13-0.82). For CRC, CCR5 correlated with left-sided tumors and liver metastases (P=0.040 and P= 0.039 respectively). As for CRLM, no correlation was found. Immunohistochemical profile analysis of CCR5 revealed a significant association with the male gender (P=0.049) and non-mucinous carcinomas (P< 0.001) in primary CRC. CCR5 expression revealed an association with the degree of tumor differentiation for both CRC and CRLM (P < 0.001). CCR5Δ32 might be a protective factor against CRC development and dissemination.

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Published

2021-12-15

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Weslati M, Boughriba R, Ounissi D, Hazgui M, Marghali S. The role of CCR5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population. Arch Biol Sci [Internet]. 2021Dec.15 [cited 2022Sep.28];73(4):503-12. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/6924

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