The role of DNA methylation in ageing and cancer.

The aim of the present review paper is to survey the literature related to DNA methylation, and its association with cancer and ageing. The review will outline the key factors, including diet, which modulate DNA methylation. Our rationale for conducting this review is that ageing and diseases, including cancer, are often accompanied by aberrant DNA methylation, a key epigenetic process, which is crucial to the regulation of gene expression. Significantly, it has been observed that with age and certain disease states, DNA methylation status can become disrupted. For instance, a broad array of cancers are associated with promoter-specific hypermethylation and concomitant gene silencing. This review highlights that hypermethylation, and gene silencing, of the EN1 gene promoter, a crucial homeobox gene, has been detected in various forms of cancer. This has led to this region being proposed as a potential biomarker for diseases such as cancer. We conclude the review by describing a recently developed novel electrochemical method that can be used to quantify the level of methylation within the EN1 promoter and emphasise the growing trend in the use of electrochemical techniques for the detection of aberrant DNA methylation.

Associations of XRCC1 S326C (rs25487) gene Polymorphism in Myelodysplastic syndrome / Эрүүл мэндийн лаборатори

Introduction@#Base excision repair (BER) is mainly responsible for the correction of small base changes of DNA damage. BER pathway involved many enzymes including OGG1 and XRCC1. The defective DNA repair is associated with an increased risk of various cancers including hematologic malignancies-leukemia and myelodysplastic syndrome (MDS). However, it is deniably these polymorphisms alter the susceptibility and clinical outcome of MDS patients.@*The aim@#This study was to evaluate the impact of polymorphisms in gene encoding one protein of BER system: XRCC1 Arg399Gln in MDS and healthy population.@*Methods@#In this study, we recruited 60 health control group [median 47.9 years, 9 MDS subjects [median 56.6 years] were included in this study. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Allele and genotype frequencies were calculated by direct counting.@*Result@#The frequencies of genotypes of XRCC1 Arg399Gln were as follows: Arg /Arg 1 (11%), Arg/Gln 6 (66%), Gln/Gln 2 (22%) in MDS and Arg /Arg 18.4%, Arg/Gln40%, Gln/Gln41.6% in health control for XRCC1 Arg399Gln. The result revealed that genotypes Arg399Gln increased the risk of MDS@*In conclusion@#this study is the first to analyze XRCC1 SNPs and their associated risk of MDS in Mongolian samples. To fully understand the role of DNA damage and DNA repair in the MDS, prospective studies are needed and other genes (OGG1 Ser326Cys, MUTYH Gln324His, APE Asp148Glu) of base excision repair pathway should be analyzed.

Dietary isoflavone intake is associated with a reduced risk of myelodysplastic syndromes.

Isoflavones have been suggested to have protective effects on certain cancers. However, the association of soya foods or dietary isoflavones with the risk of myelodysplastic syndromes (MDS) has not been examined. Thus, the aim of this hospital-based case-control study undertaken in China in 2012-2013 was to investigate the association between dietary isoflavone intake and MDS risk. The analysis included 208 cases aged 19-85 years with MDS and 208 controls individually matched to the cases by sex, birth quinquennium and residential locality. Information on habitual food intakes, including nine items of soya foods, was sought from in-person interviews using a validated 107-item FFQ. Dietary intakes of daidzein, genistein, glycitein and total isoflavones were estimated using the 2008 US Department of Agriculture Isoflavone Database. OR were calculated from conditional logistic regression after adjustment for potential confounding by demographics, lifestyle and dietary factors. The mean daily intake of total isoflavones was 19·0 mg in cases and 23·0 mg in controls. Dietary intake of isoflavones was inversely associated with the risk of MDS. The adjusted OR in the highest tertile compared with the lowest tertile of intake were 0·43 (95 % CI 0·21, 0·85) for daidzein, 0·36 (95 % CI 0·18, 0·74) for genistein, 0·49 (95 % CI 0·25, 0·97) for glycitein and 0·40 (95 % CI 0·20, 0·81) for total isoflavones. The findings suggest that higher dietary intake of isoflavones is associated with a reduced risk of MDS in a Chinese population.

Combined analysis of DNA methylation and cell cycle in cancer cells.

DNA methylation is a chemical modification of DNA involved in the regulation of gene expression by controlling the access to the DNA sequence. It is the most stable epigenetic mark and is widely studied for its role in major biological processes. Aberrant DNA methylation is observed in various pathologies, such as cancer. Therefore, there is a great interest in analyzing subtle changes in DNA methylation induced by biological processes or upon drug treatments. Here, we developed an improved methodology based on flow cytometry to measure variations of DNA methylation level in melanoma and leukemia cells. The accuracy of DNA methylation quantification was validated with LC-ESI mass spectrometry analysis. The new protocol was used to detect small variations of cytosine methylation occurring in individual cells during their cell cycle and those induced by the demethylating agent 5-aza-2'-deoxycytidine (5AzadC). Kinetic experiments confirmed that inheritance of DNA methylation occurs efficiently in S phase and revealed a short delay between DNA replication and completion of cytosine methylation. In addition, this study suggests that the uncoupling of 5AzadC effects on DNA demethylation and cell proliferation might be related to the duration of the DNA replication phase.