Promoter Hypermethylation of Wnt/β-catenin Signaling Pathway Inhibitor WIF-1 Gene and its Association with MTHFR C677T Polymorphism in Patients with Colorectal Cancer
| Autor: | Ahmad Jalilvand, Mohammad Soleiman Soltanpour |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Oman Medical Journal, Vol 35, Iss 3, Pp e131-e131 (2020) |
| Druh dokumentu: | article |
| ISSN: | 1999-768X 2070-5204 |
| DOI: | 10.5001/omj.2020.49 |
| Popis: | Objectives: Colorectal cancer (CRC) is a common malignancy with a high rate of mortality. The dysregulation of genes involved in the Wnt/β-catenin signaling pathway is a common finding in cancers. Wnt-inhibitory factor-1 (WIF-1) suppresses the Wnt/β-catenin signaling pathway and its inactivation by genetics and epigenetic changes may cause cancer. We investigated the DNA methylation status of the WIF-1 gene in patients with CRC and its interaction with MTHFR C677T polymorphism, a known modifier of methylation reaction. Methods: We investigated 50 cancerous tissues and the adjacent non-cancerous tissue. Genomic DNA was extracted using a commercial kit and was treated by sodium bisulfite. Methylation-specific PCR was used for methylation analysis, and restriction fragment length polymorphism PCR to analyze the C677T polymorphism of the MTHFR gene. Results: The frequency of WIF1 promoter DNA methylation was significantly higher in cancerous tissue than adjacent non-cancerous tissue (52.0% vs. 8.0%; p < 0.001). WIF1 promoter DNA methylation status showed a significant association only with tumor location (p =0.009). Carriers of TT genotype and T allele of MTHFR C677T polymorphism had a significantly higher frequency of unmethylated WIF1 gene than methylated WIF-1 gene in cancerous tissue (p =0.025 and p =0.001, respectively). Conclusions: Promoter DNA hypermethylation of the WIF-1 gene is a significant risk factor for CRC development, which was significantly associated with tumor location only. The significant association of TT genotype and T allele of MTHFR C677T polymorphism with unmethylated WIF-1 gene suggests a protective role for this common polymorphism against methylation-induced development of CRC. |
| Databáze: | Directory of Open Access Journals |
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