Genetics of colorectal cancer (Review)

There is an increasing awareness of the genetic basis of colon cancer and the application of gene therapy. The most commonly altered oncogenes are c-Ki-ras and c-myc, with less frequent involvement of c-src and c-erb. The loss of heterozygosity (LOH) on chromosome 5q has been frequently associated with adenomas, occurring on 17q, 18q, 1p35, 8p22 and 22q11-13 loci. This results in a loss of tumor suppressor gene for these chromosomes. The LOH on 5q was noted on the adenomatous polyposis coli (APC) and the gene on chrome-some 5 was mutated in over 55% cases of colorectal cancer, termed mutated in colon cancer (MCC). MCC is regarded as a tumor suppressor gene which is responsible for the initiation of colon cancer. The deleted in colon cancer gene (DCC) on 18q21 is a common cause of adenomas and the LOH on 17q in p53 gene are frequently seen in bowel cancer. Comparison of frequency with which tumor suppressor and oncogenes are altered in the adenomas and carcinomas suggests that there is a preferred order for their occurrence in the adenoma-carcinoma sequence. Our studies indicate that supplement with tumor suppressor oncoprotein may open a new avenue for gene therapy of colorectal cancer but steps in the identification of the gene(s) await further exploration.