title: Polymorphism in folate- and methionine-metabolizing enzyme and aberrant CpG island hypermethylation in uterine cervical cancer.
abstract: 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 (CI) 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.
  
  
  CONCLUSIONS
  These findings suggest that there is a possible interaction between epigenetic and genetic factors in uterine cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University, 28 Yungun-Dong, Chongno-Ku, Seoul, 110-744, South Korea.
authors.forename: Sokbom
authors.initials: S
authors.lastname: Kang
authors.forename: Jae Weon
authors.initials: JW
authors.lastname: Kim
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Noh Hyun
authors.initials: NH
authors.lastname: Park
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Song
authors.forename: Soon Beom
authors.initials: SB
authors.lastname: Kang
authors.forename: Hyo Pyo
authors.initials: HP
authors.lastname: Lee
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D017766:Acid Anhydride Hydrolases / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D017766:Acid Anhydride Hydrolases; D015820:Cadherins; D005492:Folic Acid; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase