71P - Single nucleotide polymorphisms in the folate metabolic pathway genes and global DNA methylation in ovarian cancer

Background

Ovarian cancer is the most common cause of death from gynecological malignancies. In the early stages, women are generally asymptomatic or have non-specific symptoms, making early-stage ovarian cancer undiagnosed. The different investigations reported the effect of polymorphisms in folate metabolism genes on ovarian cancer risk in different ethnicities. The aim of the current study was to analyze associations between the polymorphisms of key folate metabolism enzyme genes, methylene tetrahydrofolate reductase (MTHFR) and 5,10-methylenetetrahydrofolate dehydrogenase (MTHFD1) (C677T and G1958A, respectively) and ovarian cancer risk in Georgia. In addition, we assessed DNA methylation levels in ovarian cancer patients with polymorphic variants of these genes.

Methods

30 cancer patients and 30 healthy controls were included in this study. All patients and controls provided informed consent before being enrolled in the study. This study was approved by the Ethics Committee of the Tbilisi State Medical University. Genomic DNA was isolated from peripheral blood using a commercial kit (Qiagen, USA). Single Nucleotide Polymorphism (SNP) genotyping was performed using TaqMan Assay (Thermo Scientific, USA). Global DNA methylation was analyzed using the Global DNA Methylation Assay Kit (Abcam, MA, USA).

Results

The results suggest that there was a high association between MTHFD1 gene G1958A variant and the risk of ovarian cancer in Georgian patients (p<0.001). No statistically significant differences in allele and genotype frequencies of MTHFR gene C677T SNP were observed between patients and controls (p > 0.05). In addition, global DNA methylation in individuals with CT+TT genotypes were found to be reduced compared to CC genotypes in respect to the C677T variant of MTHFR gene.

Conclusions

In our study, we did not find any association between the MTHFR gene C677T polymorphism and ovarian cancer, however the AA genotype of MTHFD1 gene G1958A variant associated with increased risk of ovarian cancer. We, also, found that CT and TT genotypes of MTHFR gene C677T variant are associated with altered DNA methylation in ovarian cancer patients.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

This study was supported by the Shota Rustaveli National Science Foundation of Georgia (grant number #FR-21-17599).

Disclosure

All authors have declared no conflicts of interest.