1887

Abstract

Abstract

It has been postulated that dietary components, in conjunction with the presence of susceptibility genes, can influence the epigenome, altering genetic expression and potentially modifying colorectal cancer (CRC) as well as Alzheimer’s disease (AD) risk. The aim of two ongoing projects is to investigate the interaction of dietary components (folate levels) with genetic susceptibility (polymorphisms of genes involved in the folate metabolic pathway) in influencing the methylation levels of genes critical for colon cancer or for neurodegeneration. We are currently analyzing the methylation status of CRC related genes including RASSF1A, MGMT, APC, hMLH1, and CDKN2A in the DNA obtained from epithelial cancerous cells isolated from either early or late stage CRC tissues through immuno-magnetic method, in order to evaluate the association between methylation and clinicopathological features. Promoter methylation profiles are evaluated by means of Methylation-Sensitive High-Resolution Melting (MS-HRM) technique. Results on a subgroup of 30 CRC patients suggest that APC is the most frequently methylated gene in our cohort, and all the other genes are found to be methylated in approximately 20-25% of the cases. Several CRC patients had elevated plasma Hcy levels (above the normal range), consistent with a condition of impaired one-carbon metabolism. We also screened blood DNA from 20 late-onset AD patients, 20 healthy controls and 20 individuals with Mild Cognitive Impairment (MCI) for CpG methylation analyses in the promoter of the β-secretase gene (BACE1). Our epigenetic analysis revealed that the BACE1 gene might be subject to epigenetic regulation due to methylation/demethylation processes of different CpG islands. The outcomes of these studies comprise more knowledge of predisposing conditions (diet, genetic variants) to develop colon cancer or neurodegeneration with the possibility to undergo a primary prevention, moreover to get information on epigenetic biomarkers associated with susceptible individuals, easily detectable and useful to design a precocious diagnostic tool.

Loading

Article metrics loading...

/content/papers/10.5339/qproc.2012.mutagens.3.36
2012-03-01
2019-10-19
Loading full text...

Full text loading...

http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.mutagens.3.36
Loading
  • Received: 09 May 2012
  • Accepted: 09 May 2012
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error