Polymorphism in folate- and methionine-metabolizing enzyme and aberrant CpG island hypermethylation in uterine cervical cancer

Objective. This study was conducted to explore the association between the CpG island hypermethylation of tumor-associated genes and the polymorphisms of methyl group metabolizing enzymes in uterine cervical cancer. Methods. We analyzed CpG island hypermethylation in 15 genes (APC, CDH1, COX2, DAPK, FHIT, GSTP1, HLTF1, hMLH1, MGMT, p14, p16, RASSF1A, RUNX3, THBS1, and TIMP3) and its association with the methylene-tetrahydrofolate reductase (MTHFR) C677T and A1298C and the methionine synthase (MS) A2756G polymorphisms in 82 Korean women with uterine cervical cancer. Results. All uterine cervical cancer samples had at least one gene methylated. The average number of methylated genes was lower in patients with the heterozygous genotype of MTHFR and MS than in those with the common homozygous genotype, although this difference was not significant. The MTHFR 677 CT genotype was significantly associated with the decreased promoter hypermethylation of O-6- methylguanine DNA methyltransferase (MGMT) (OR = 0.22, 95% confidence interval (C1) 0.07-0.70, P = 0.011). However, the MTHFR C677T and A1298C and the MS A2756G polymorphisms were not associated with an increased risk of uterine cervical cancer. Conclusion. These findings suggest that there is a possible interaction between epigenetic and genetic factors in uterine cervical cancer. (C) 2004 Elsevier Inc. All rights reserved.