title: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and promoter methylation in cervical oncogenic lesions and cancer.
abstract: The aim of this study was to investigate the role of methylenetetrahydrofolate reductase (MTHFR) polymorphisms and MTHFR methylation pattern in cervical lesions development among women from Romania, a country with high prevalence of human papillomavirus (HPV) cervical infections. To achieve this goal, blood samples and cervical cytology specimens (n = 77)/tumour tissue specimens (n = 23) were investigated. As control, blood and negative cytological smears (n = 50) were used. A statistically significant association was found between T allele of C677T polymorphism and cervical lesions, heterozygote women presenting a threefold increased risk (normal/cervical lesions and tumours: wild homozygote 34/41 (0.68/0.41), heterozygote 14/51 (0.28/0.51), mutant homozygote 2/8 (0.04/0.08); OR = 3.081, P = 0.0035). Using χ square test for the control group, the HPV-negative and HPV-positive patients with cervix lesions, a significant correlation between viral infection and T allele of C677T polymorphism (P = 0.0287) was found. The MTHFR promoter was methylated in all HGSIL and tumour samples, significant differences being noted between HPV-positive samples, control group and cases of cervical dysplastic lesions without HPV DNA (P < 0. 0001) and between samples from patients with high-risk (hr)HPV versus low-risk (lr)HPV (P = 0.0026). No correlations between polymorphisms and methylation were observed. In Romania, individuals carrying T allele are susceptible for cervical lesions. MTHFR promoter methylation is associated with cervical severity lesions and with hrHPV.
authors: Viral Genetic Engineering Laboratory, Romanian Academy Stefan S. Nicolau Virology Institute, Bucharest 030304, Romania.
authors: Anca
authors: A
authors: Botezatu
authors: Demetra
authors: D
authors: Socolov
authors: Iulia V
authors: IV
authors: Iancu
authors: Irina
authors: I
authors: Huica
authors: Adriana
authors: A
authors: Plesa
authors: Carmen
authors: C
authors: Ungureanu
authors: Gabriela
authors: G
authors: Anton
mesh_terms: D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D019175:DNA Methylation; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000821:virology; D055815:Young Adult
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)