TET enzymes and 5hmC epigenetic mark: new key players in carcinogenesis and progression in gynecological cancers.

DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine (5mC). In general, DNA methylation in cancer is associated with the repression of the expression of tumor suppressor genes (TSG) and the demethylation with the overexpression of oncogenes. DNA methylation was considered a stable modification for a long time, but in 2009, it was reported that DNA methylation is a dynamic modification. The Ten-Eleven-Translocations (TET) enzymes include TET1, TET2, and TET3 and participate in DNA demethylation through the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC). The 5hmC oxidates to 5-formylcytosine (5fC) and 5-carboxylcitosine (5caC), which are replaced by unmodified cytosines via Thymine-DNA Glycosylase (TDG). Several studies have shown that the expression of TET proteins and 5hmC levels are deregulated in gynecological cancers, such as cervical (CC), endometrial (EC), and ovarian (OC) cancers. In addition, the molecular mechanisms involved in this deregulation have been reported, as well as their potential role as biomarkers in these types of cancers. This review shows the state-of-art TET enzymes and the 5hmC epigenetic mark in CC, EC, and OC.

Ethnic variation of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase (MTHFR) gene in southwestern Mexico.

In this study, we examined the distribution of genotype and allele frequencies of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase gene (MTHFR) in two ethnic groups in the State of Guerrero, Mexico, which were compared with those of the Mestizo population of the region. A comparative study was conducted on 455 women from two ethnic groups and a group of Mestizo women of the State of Guerrero, Mexico: 135 Nahuas, 124 Mixtecas, and 196 Mestizas. Genotyping of both polymorphisms were performed by using polymerase chain reaction-restriction fragment length polymorphism methods. We found that the 677TT genotype was more frequent in Nahua and Mixteca women compared to Mestiza women (P = 0.008), and the most prevalent genotype in both ethnic groups was the 1298AA genotype (P < 0.001). We also compared the 677T allele frequency obtained from the groups studied with the frequencies reported in other ethnic groups of Mexico (Huichol, Tarahumara, and Purepecha). There were significant differences between the three ethnic groups compared to Nahuas (Huicholes, P = 0.004; Tarahumaras, P < 0.001; Purepechas, P = 0.042). Our results indicated significant differences in the frequencies of the C677T and A1298C polymorphisms between the two ethnic groups and the Mestizo population of the State of Guerrero. In addition, we found strong differences with other ethnic groups in Mexico. These results could be useful for future studies investigating diseases related to folate metabolism, and could help the government to design specific nutrition programs for different ethnic groups.