MTHFR C677T polymorphisms are associated with aberrant methylation of the IGF -2 gene in transitional cell carcinoma of the bladder

The purpose of this study was to determine the relationship between methylation status of the insulin - like growth factor 2 ( IGF -2) gene and methylenetetrahydrofolate reductase ( MTHFR) C677T gene polymorphisms in bladder transitional cell carcinoma tissues in a Chinese population. The polymorphisms of the folate metabolism enzyme gene MTHFR were studied by restrictive fragment length polymorphism (RFLP). PCR - based methods of DNA methylation analysis were used to detect the CpG island methylation status of the IGF -2 gene. The as -sociation between the methylation status of the IGF -2 gene and clinical characteristics, as well as MTHFR C677T polymorphisms, was analyzed. Aberrant hypomethylation of the IGF -2 gene was found in 68.3% bladder cancer tissues and 12.4% normal bladder tissues, respectively, while hypomethylation was not detected in almost all nor -mal bladder tissues. The hypomethylation rate of the IGF -2 gene in cancer tissues was significantly higher in pa -tients with lymph node metastasis than in those without lymph node metastasis (46.3% vs 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smok -ing, alcohol consumption and green tea consumption. After adjusting for potential confounding variables the vari -ant allele of MTHFR C677T was found to be associated with hypomethylation of the IGF -2 gene. Compared with wildtype CC, the odds ratio was 4.33 (95% CI=1.06 -10.59) for CT and 4.95 (95% CI=1.18-12.74) for TT. MTHFR 677 CC and CT genotypes might be one of the reasons that cause abnormal hypomethylation of the IGF -2 gene, and the aberrant CpG island hypomethylation of the IGF -2 gene may contribute to the genesis and progression of bladder transitional cell carcinoma.