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.