Abstract
BackgroundDNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing.ResultsWe analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio – the latter is also a known risk factor for colon cancer development.ConclusionsOur study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer.
Highlights
DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer
Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and may offer potential as a putative biomarker for colorectal cancer
This study proposes to look at the gene specific methylation patterns of MYOD-1 gene within the colon in normal individuals, in an attempt to understand its relationship with known risk factors of colon cancer including age, lifestyle and anthropometric measures (waist to hip ratio (WHR))
Summary
DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. We have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing. Several studies have demonstrated hypermethylation of this gene in tumour tissue and to a lesser extent in the normal adjacent colon [8,9]. The function of this gene is of particular interest as it is a specific muscle regulator, it is capable of inducing myogenesis in other cell types and may interact with other stem cell lineages [10,11]. Ahuja et al [8] have shown significant hypermethylation of MYOD-1 in colon cancer tissue compared to adjacent normal mucosa and this increases with in age
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