Chronic colonic diseases are divided into Inflammatory Bowel Diseases (IBD) which include Ulcerative Colitis (UC) and Crohn's Disease (CD) , colorectal cancer and colonic polyposis syndromes which include familial Adenomatous polyposis (FAP) and Peutz Jegher syndrome. The risk for Ulcerative Colitis associated Colorectal Cancer is increased at least 2 folds compared to the normal population. Colorectal cancer is observed in 5.5% -13.5% of all patients with Ulcerative colitis and 0.4%- 0.8% of patients with Crohn’s disease. Colorectal cancer remains the second leading cause of cancer death in USA. It is considered to be the fourth most common malignant neoplasm representing 6.1% of cancers in Egypt The search for IBD-susceptibility genes has resulted in the identification of several loci with potential relevance to IBD etiology. These include IBD1 (MIM 266600), a putative CD-susceptibility locus that maps to the pericentromeric region of chromosome 16 and IBD2 (MIM 602458), mapped to a 41-cM region, on chromosome 12, surrounding the D12S83 marker and implicated in both CD and UC The identification of 5q31-33 and 19p13 as potential locations for IBD-susceptibility genes is of particular interest in view of the biology of the genes known to map within these regions. One of the genes causing susceptibility to CD was recently identified as the CARD15/NOD2 gene The etiology of colorectal cancer is unknown but appears to be multifactorial in origin .The relative risk of developing colorectal cancer is increased in the first-degree relatives of affected patients. The defect is in the adenomatous polyps coli (APC) gene, which is located on chromosome 5 at locus q21.Defective mismatch repair (MMR) genes located on chromosomes 2, 3, and 7. PTEN is a candidate tumor suppressor gene that has been isolated and localized at chromosomal band 10q23 The high hope of genetic medicine for 30 years has been to develop a way of using recombinant DNA techniques to treat patients through the genes involved in their diseasesExamples for gene therapy:-I) Immune Stimulation :- A) Utilization of human leukocyte antigen (HLA) to stimulate T-cell response. B) Utilization of cytokines to stimulate T cell response. C) Vaccination against tumour-specific antigens. II) Mutant gene correction III) Virus-directed enzyme prodrug therapy. IV) Oncolytic virus therapy. V) Inhibitors of angiogenic growth-factors and their receptors Gene therapy for colon cancer is still at an early stage of development. Preclinical studies have prompted several phase I trials. As our understanding of the molecular biology of cancer increases, gene therapy is likely to have an increasingly important role in the expanding array of treatment options for colon cancer.