MOLECULAR-GENETICS OF COLON-CANCER

Colorectal cancer remains a major health problem. Few therapies are ef fective apart from surgery, and survival has increased little in recen t years. This is despite the fact that screening by colonoscopy can po tentially remove nearly all colorectal tumours before they become mali gnant. Molecular genetics has identified some inherited mutations (suc h as at APC and the mismatch repair loci) that predispose to colon can cer and some somatic mutations (such as at APC and p53) that cause spo radic colon tumours. We review the likely role of these and other gene s in colorectal tumorigenesis. We also highlight areas of relative ign orance in colon cancer and emphasise that many important genes, especi ally those that cause invasion and metastasis, remain to be identified . Colorectal cancer is, however, a well characterised tumour, as regar ds both its natural history and its histopathology; there are conseque ntly good prospects for advances in colon cancer genetics, with probab le benefits for its treatment. We anticipate: (a) that new genes predi sposing to colon tumours, including those conferring relatively minor risks, will be characterised; (b) genes and proteins important in inva sion and metastasis will be identified; (c) the network of protein int eractions in which molecules such as APC are involved will be elucidat ed; (d) large-scale studies of somatic mutations in tumours will provi de accurate predictions of prognosis and suggest optimal therapeutic r egimens; and (e) new potential targets for therapy will be identified. Whilst molecular genetics is by no means sufficient for progress in p reventing and treating colon cancer, it is a necessary and central par t of such advances.