Relationships among MTHFR a1298c Gene Polymorphisms and Methylation Status of Dact1 Gene in Transitional Cell Carcinomas

Objectives: The purpose of this study was to determine the relationship between methylation status of theDact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population.
Methods: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragmentlength polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine theCpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed.
Results: aberrantmethylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylationrate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than inthose without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrantDNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green teaconsumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was foundto be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95%CI: 1.06–10.59) for AC and 4.95 (95% CI: 1.18–12.74) for AA. The N stage in TNM staging and the occurrence oflymph node metastasis were associated with an MTHFR 1298 AA+AC genotype (P<0.05).
Conclusion: MTHFR1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpGisland methylation of which is closely related to the genesis and progression of transitional cell carcinoma.