Methylation of the MGMT and p16 genes in sporadic colorectal carcinoma and corresponding normal colonic mucosa
Lukasz Krakowczyk, Joanna Katarzyna Strzelczyk, Brygida Adamek, Marzena Zalewska-Ziob, Jerzy Arendt, Stanislaw Poltorak, Boguslaw Maciejewski, Andrzej Wiczkowski
Med Sci Monit 2008; 14(10): BR219-225
Colorectal cancer, one of the most aggressive cancers, occurs with a high incidence in most countries. The usual treatment is surgery and subsequent chemotherapy and radiotherapy. Cancer development and progression is dictated by series of alterations in genes such as tumor suppressor genes, DNA repair genes, oncogenes and others. In colorectal carcinogenesis disturbances different from mutations called an epigenetic regulation are also taken into consideration. Epigenetics is defined as a modifications of the genome, heritable during cell division, which do not involve a change in the DNA sequence. In our study we analyzed methylation of CpG islands in the MGMT and p16 genes in sporadic colorectal cancers and normal corresponding colonic mucosa.
Material and Method: Fresh tissue samples were obtained from 68 patients (age of 23 to 81 years) with primary colorectal adenocarcinoma and corresponding normal tissues. We used methylation-specific polymerase chain reaction (MSP) for analysis of the methylation status of MGMT and p16.
Results: Methylation of MGMT and p16 was detected in 59% and 53% of tumors, respectively. In corresponding normal colonic mucosa methylation of MGMT was detected in 20% and p16 in 18%. The normal colon mucosa obtained from younger patients (age of <65 years) showed less methylation frequency as compared with the normal mucosa from the older ones (age of >65 years).
Conclusions: The older age and female gender are generally associated with higher methylation levels for most CpG islands in normal colonic mucosa. These results indicate that MGMT and/or p16 aberrant methylation may play an important role in colorectal cancer.
Keywords: Promoter Regions, Genetic, Intestinal Mucosa - pathology, Genes, p16, Epigenesis, Genetic, DNA Repair Enzymes - metabolism, DNA Modification Methylases - metabolism, DNA Methylation, CpG Islands, young adult, Tumor Suppressor Proteins - metabolism, Colorectal Neoplasms - pathology, Colon - pathology, Aged, 80 and over, Adult