New approaches to the role of diet in the prevention of cancers of the alimentary tract.

Cancers of the alimentary tract are, collectively, amongst the major causes of morbidity and deaths from cancer across the world today. Of the 10 million new cases of cancer diagnosed in 2000, about 2.3 million were cancers of the pharynx, oesophagus, stomach or colorectum. Nevertheless, epidemiological studies indicate that cancers of the digestive organs are also amongst the most susceptible to modification by dietary factors. International variations in incidence suggest that round three quarters of all sporadic colorectal cancers are attributable to diet. Even within the relatively uniform environment of the European Union, there are variations in the incidence of colorectal and oesophageal cancers of about two- and six-fold, respectively. Carcinomas of the alimentary tract arise from epithelial cells via distinct sequences of neoplastic change, which require a large fraction of an individual's lifespan. The best characterised of these is the adenoma-carcinoma sequence of colorectal carcinogenesis, in which progressive loss of differentiation and normal morphology in a growing lesion is associated with the acquisition of somatic mutations, and of aberrant methylation of CpG-islands, leading to gene silencing. These molecular events are accompanied by functional changes, including increased mitosis and evasion of apoptosis. There is little evidence that diet exerts its effects primarily through food-borne carcinogens that can be identified and eliminated from the food-chain. It is far more probable that the adverse effects of diet are caused largely by over-consumption of energy, coupled with inadequate intakes of protective substances, including micronutrients, dietary fibre and a variety of phytochemicals. The latter are biologically active secondary plant metabolites, many of which modify cell proliferation and induce apoptosis in vitro. There is growing evidence that such effects also occur in vivo, and that they can suppress the progress of neoplasia. Carcinomas of the oesophagus, stomach and colon all appear to be partially preventable by diets rich in fruits and vegetables. Plant foods contain a variety of components including micronutrients, polyunsaturated fatty acids, and secondary metabolites such as glucosinolates and flavonoids, many of which can inhibit cell proliferation and induce apoptosis, and which may well act synergistically when combined in the human diet. The future challenge is to fully characterise and evaluate these effects at the cellular and molecular level, so at to exploit their full potential as protective mechanisms for the population as a whole.