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The cause of colorectal cancer

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      Abstract

      Colorectal cancer continues to represent one of the major causes of cancer-related morbidity in all western countries. A review has been made of the main aetiological factors which have been related to colorectal cancer development with particular attention being focused on: a) new advancements in molecular biology, and b) the interaction between genetic predisposition and environmental factors. Worldwide, approximately 900,000 cases of colorectal malignancies have been diagnosed in 1996 and this accounts for 8.5% of all new cases of cancer. Crude incidence rates range from 0.6 – 5.0 cases/100,000/year in Senegal and India to 50–70 cases in developed countries. Environmental factors, such as meat, saturated fat, low physical activity, obesity, smiking, alcoholic beverages, and inflammatory bowel diseases seem to increase the risk of colorectal cancer. In contrast, fruit, vegetables, fibre, antioxidant vitamins, calcium, folate, physical exercise and non-steroidal anti-inflammatory drugs seem to show a orotective effect. For some of these factors, the molecular basis of their mechanism of action begins to be elucidated. Colorectal cancer develops from benign precursors, the adenomatous polyps; there is extensive evidence that polyps transform into cancer in a stepwise manner, and that several molecular abnormalities (mutations of oncogenes, inactivation of tumour suppressor genes and microsatellite instability) accompany and, somehow, determine colorectal tumourigenesis. Two major Hereditary Colorectal Cancer syndromes — Familial Adenomatous Polyposis and Hereditary Non polyposis Colorectal Cancer — have been described and characterized at molecular levels; it is estimated that these inherited conditions might account for up to 5% of all large bowel malignancies. Familial colorectal cancer remains undefined and is presumably due to multifactorial inheritance. Recently, identified germline mutations (such as l1307K in the APC gene) might account for a fraction of these familial cases, at least in some populations. At variance with many other tumours, the aetiology and pathogenesis of colorectal cancer have been partially clarified, so that we are now in the position to take preventive measures and to design surveillance programmes which might lead to a certain reduction in incidence and mortality. However, since many of the aetiological factors are strictly related to modern customs and lifestyle, they will be difficult to eradicate; this awareness should stimulate further investigations in this exciting field of research.

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