Colorectal carcinogenesis involves genetic and epigenetic alterations
that cause aberrant gene function. Recent progress in the knowledge of
epigenetics has had a profound impact on the understanding of mechanisms
leading to colorectal cancer, and consequently the development of new
strategies for diagnosis and management of colorectal cancer.
A close relationship has been confirmed between the number of the
affected individuals and their relatives of different degree in the same
family. One of the accused mechanisms is DNA methylation that may be
affected by many factors shared by some or all family members.
Expression of one or more genes, even if still unkown, will be affected in a
subclinical state. Early detection of these changes will be a challenge in
both diagnosis and treatment.
The present study aimed to detect the methylation status of APC and
KEAP1 promoters and their relationship with various clinicopathological
parameters, including the gene expression level, in the blood of colorectal
cancer patients, in order to evaluate the potential use of such epigenetic
markers in diagnosis of colorectal cancer and also to study the relationship
between the gene expression within the patients and their first degree
relatives (FDRs) to allow early detection and treatment whenever possible.
This study included 30 colorectal cancer patients and 30 FDRs to
these patients treated at the General surgery department, Benha University
Hospital &15 apparent healthy volunteers.
All patients included in the study were subjected to history taking,
clinical examination, laboratory, radiological investigations and Detection of promotor methylation status of APC and KEAP1 using methylation specific
PCR and detection of gene expression level of APC and KEAP1 genes in
blood samples.
The results of the present study showed that APC methylated
promoter was detected in 87 % of rectal cancer patients and all colon
cancer patients, 27 % & 13% of FDR cases of rectal and colon cancer
patients respectively; while, all healthy subjects were unmethylated.
Moreover, the KEAP1 promoter was found to be methylated in all
rectal cancer patients & 20 % of colon cancer patients, 27% of either
FDR cases of rectal and colon cancer patients; while, all healthy subjects
were unmethylated.
Using a panel of both genes revealed that at least one gene was
methylated in 13 % & 80% of rectal cancer patients & colon cancer
patients respectively, 53% & 40% of FDR cases of rectal and colon cancer
patients respectively; while, all healthy subjects were unmethylated.
Furthermore, our study revealed that the methylation levels of APC,
KEAP1 & APC/KEAP1 panel in CRC group were significantly elevated
as compared to the methylation levels in both their FDRs or control
groups. |
