Genetic predisposition to gastric cancer

Wide variations exist in the incidence of gastric cancer between populations. In Japan, the incidence is as high as 80 per 100 000 males, whilst in most African states the overall incidence is only 5 per 100 000. In Europe, incidence rates are between 20 and 40 per 100 000, and females have about half the male gastric cancer risk.1 Approximately 90% of gastric cancers are adenocarcinomas. These can be classified according to their differentiation or according to the histomorphological classification of Lauren, which divides the tumours into \`intestinal' and \`diffuse'.2 Intestinal tumours are usually exophytic, often ulcerating, and are associated with intestinal metaplasia of the stomach. Diffuse tumours are poorly differentiated infiltrating lesions which lead to thickening of the stomach ( linitis plastica ). Patients with diffuse-type tumours have a worse prognosis than those with an intestinal type. Intestinal cancers appear to be more common in proximal (fundus) localized tumours than in distal lesions, while diffuse, poorly differentiated tumours predominate in younger patients.3 Interestingly, the diffuse type of gastric carcinoma demonstrates a nearly equal sex ratio, compared with a male preponderance in the intestinal form. The varying rates in different populations, coupled with studies of migrants, strongly implicate environmental factors in the aetiology of gastric cancer. These factors include the level of antioxidants such as vitamin E and ascorbic acid in the diet, and the role of Helicobacter pylori .4–6 In addition to environmental factors, there is increasing evidence that some gastric cancers are caused by an inherited predisposition. Identification of these predisposition genes should be useful for identifying those at high risk, as well as helping to provide a model for gastric carcinogenesis in general. Evidence for a genetic predisposition to gastric cancer comes from both epidemiological studies and case reports of gastric cancer families. Systematic case-control …