Distinct Pattern Of Epigenetic DNA Modification In Leukocytes From Patients With Colorectal Carcinoma And Individuals With Precancerous Conditions, Benign Adenoma And Inflammatory Bowel Disease; A Link To Oxidative Stress

A characteristic feature of malignant cells, including colorectal cancer cells, is a profound decrease in level of 5-hydroxymethylcytosine, product of 5-methylcytosine oxidation by TET enzymes. This study included four groups of subjects: healthy controls, and patients with inflammatory bowel disease (IBD), benign polyps and colorectal cancer. Patients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine than the controls. A similar tendency was also observed for 5-hydroxymethyluracil level. Patients with IBD showed the highest levels of 5-formylcytosine and 8-oxo-7,8-dihydro-2-deoxyguanosine of all study subjects, and individuals with colorectal cancer presented with the lowest concentrations of vitamin C and A. Expressions of TET1 and TET2 turned out to be the highest in IBD group. To the best of our knowledge, this is the first study to show that healthy subjects, individuals with precancerous conditions and colorectal cancerpatients present with distinct specific patterns of epigenetic modifications in leukocyte DNA.