Molecular biology of colorectal neoplasia.

Leading article -Molecular biology series Molecular biology of colorectal neoplasiaLarge bowel cancer is a major cause of morbidity and mortality in the western world.In England and Wales approximately 8500 men and 9000 women die of the disease every year.'Yet despite this, relatively little is known of its pathogenesis in the vast majority of sporadic cases.In 1954, Armitage and Doll proposed that common cancers arise as a result of the accumulation of as many as seven events.2Most scientists now believe that the molecular substrate for these critical events in tumorigenesis are genes that regulate cell proliferation and differentiation -that is, oncogenes and tumour suppressor genes.Alterations to the expression or structure of these genes may result in the perturbation of cell growth, which is the hallmark of neoplasia.The past 10 years has seen an explosion in our knQwledge of the molecular biology ofcancer, and nowhere has this been as exciting as in the field of large bowel cancer.Research into colorectal tumours has directly or indirectly contributed to the discovery of three new tumour suppressor genes; APC, DCC, and p53, the latter probably representing the common- est genetic abnormality so far described in human cancer.3Therefore, despite being unclear about the environmental agents that promote genetic changes in the large bowel, in few other tumour systems are we as close to identifying the critical events which underlie malignant, neoplastic behaviour as we are in colorectal cancer.