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.

Differential gene hypermethylation in genital lichen sclerosus and cancer: a comparative study

“…10,47,51 This suggested dichotomous pathway to cancer via LS or via HPV 20 is not supported by observed differences in hypermethylation of any of the genes between the HPV-positive and HPV-negative vulvar and penile tumours included in this study and in previous reports. 30,33 The association between the presence of HPV and the hypermethylation of the methylenetetrahydrofolate reductase (MTHFR) or paternally expressed gene 3 (PEG3) genes found in cervical cancer 52,53 is not shown by the genes analysed here in vulvar and penile cancer. 33,[54][55][56] Other local risk factors associated with LS, such as phimosis and poor hygiene, have also been postulated to predispose to malignancy, rather than LS itself and the presence of HPV.…”

Gene-Specific Methylation Analysis in Thymomas of Patients with Myasthenia Gravis

“…It is revealing that the MTHFR gene is regulated by promoter methylation and an increased MTHFR promoter methylation has been observed in several human diseases, such as cardiovascular and renal diseases [18,19], male infertility [20,21,22], and preeclampsia [23]. Moreover, it is also emerging that MTHFR hypermethylation could be involved in cancer formation; in fact, a correlation between MTHFR hypermethylation and lung cancer or cervical cancer lesions was observed [15,24]. …”

MTHFR promoter hypermethylation may lead to congenital heart defects in Down syndrome

“…The CpG islands present in the 5'-untranslated promoter region of MTHFR; from + 30 to 184 from the TSS (transcription start site) was studied. This region contains seven CpG islands and the methylation levels of these CpG islands were found to be associated with gene expression levels in human lung cancer cells (16). Table 1 shows the details of PCR reaction and primers including: the sequence of primers used, annealing temperature (Ta), amplicon length, the location of promoter region studied and the number of CpG islands it contained.…”