The Relationship between the Methylenetetrahydrofolate Reductase Genotypes and the Methylation Status of the CpG Island Loci, LINE-1 and Alu in Prostate Adenocarcinoma

ABSTRACT

BACKGROUND: Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR), in association with the influence of MTHFR upon DNA methylation, may cause differences of the methylation profile of cancer. Thus, we investigated the relationship between the methylation status of prostate adenocarcinoma and the genetic polymorphism of MTHFR. METHODS: We examined 179 cases of prostate adenocarcinoma for determining the genotypes of MTHFR 677 and 1298, the methylation status of 16 CpG island loci and the methylation levels of the LINE-1 and Alu repeats with using polymerase chain reaction/restriction fragment length polymorphism, methylation-specific polymerase chain reaction and combined bisulphite restriction analysis, respectively. RESULTS: There was a higher proportion of the CT genotype of MTHFR 677 in the prostate adenocarcinoma than that in the normal control. The TT genotype of MTHFR 677 showed the highest frequency of methylation in six out of nine major CpG island loci, and these were which were frequently hypermethylated in prostate adenocarcinoma. The CT type showed the lowest methylation levels of LINE-1 and Alu among the MTHFR 677 genotypes. Interestingly, the CC type of MTHFR 1298 demonstrated favorable prognostic factors. CONCLUSIONS: Our study is the first to examine the methylation profile of prostate adenocarcinoma according to the MTHFR genotypes. The differences of the cancer risk, the genomic hypomethylation and the prognosis between the MTHFR genotypes in prostate adenocarcinoma should be further explored.