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 (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.
Kang
Sokbom
S
Department of Obstetrics and Gynecology, Seoul National University, 28 Yungun-Dong, Chongno-Ku, Seoul, 110-744, South Korea.
Kim
Jae Weon
JW
Kang
Gyeong Hoon
GH
Park
Noh Hyun
NH
Song
Yong Sang
YS
Kang
Soon Beom
SB
Lee
Hyo Pyo
HP
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
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