Early detection of Egyptian colorectal cancer patients using stool-based DNA markers

ABSTRACT

About 50% of the patients with colorectal cancer who are diagnosed on the basis of clinical symptom could be cured by surgery. It may be assumed that diagnosis and surgery at an earlier asymptomatic stage would allow more patients to be cured. Therefore, screening appears to be the simplest way to decrease mortality due to colorectal cancer. The emergence of molecular stool testing promises accurate and user friendly alternative to conventional methods of colorectal cancer screening. The aim of this work is to evaluate the stool-based DNA test for three genetic markers on Egyptian patients. DNA was extracted from stool and/or tissue samples collected from 45 Egyptian patients [17 colorectal cancer, 28 non-cancerous lesions and normal] the lesions include ulcerative colitis, polyps, and schistosomiasis. Mutations were detected in k-ras oncogene at codon 12 using RFLP technique, p53 gene [exons 5, 6, and 7] using SSCP technique and finally microsatellite instability [MSI] for BAT-26 locus as a marker for mismatch repair gene. The overall molecular changes using the three markers showed that 25 patients out of 45 [55.56%] exhibited mutations in one or more of the markers used. Mutations were detected in 76.46% colorectal cancer patients. In non-cancerous cases, 42.86% exhibited mutations using the same gene panel. P53 mutation recorded the highest percentage of markers used [58.8%] in cancerous cases whereas it was 42.86% in non-cancerous cases. K-ras mutations recorded about 29.4% in cancerous cases and non in non-cancerous cases. Finally, MSI at BAT-26 was only 5.9% in cancerous cases and no MSI in non-cancerous group. In conclusion, p53 may represent a golden marker for Egyptian patients with colorectal cancer and pre-malignant diseases. Using multi-target genetic panel is successfully for early detection of colorectal cancer. Finally, stool-based DNA test is a real golden method which reflect the genetic changes in the tumors