Cancers of the head and neck, stomach and pancreas are amongst the commonest cancers in the developing world and not rare in Western countries. Some of these (pituitary, pancreatic endocrine and parathyroid) make up the MEN 1 syndrome. The most important aetiological factors for the former cancers are environmental exposure to tobacco, alcohol and other substances. In a small minority of cases, mendelian inheritance plays an important role. In particular, E-cadherin (CDH1), has been found to be mutated in the germline of some individuals with diffuse gastric cancer. Germline BRCA2 and CDKN2A mutations have been identified in those with pancreas cancer, often in families with breast and ovarian cancers, and in the case of CDKN2A, cutaneous malignant melanoma. Numerous association studies have focused on polymorphisms in so-called susceptibility genes, such as GSTM1, NAT2 and, more recently, repair enzymes such as XRCC1. Overall, this avenue of research has proved to be disappointing and very little consistency has been observed in the results when different populations are studied. Nevertheless, the possibility that, in a non-familial setting, the risk of cancer can be sufficiently accurately characterized to justify preventive intervention remains a major raison d’être of genetic research into the aetiology of
of genetic factors and their possible interaction with nongenetic risk factors at these three sites.