Familial gastric cancer - aetiology and pathogenesis.

Gastric cancer is the second most common cause of cancer death worldwide. It is estimated that 5-10% of gastric cancer cases have a familial association; however, knowledge concerning the genetic predisposition to familial gastric cancer is currently limited. In this chapter we discuss what is known about the aetiology and pathogenesis of both the diffuse and intestinal forms of familial gastric cancer. We focus particularly on hereditary diffuse gastric cancer because the discovery of germ-line E-cadherin mutations in a number of affected families has opened the prospect of identifying gene carriers, with implications for clinical management. The interplay of other conventional risk factors, such as Helicobacter pylori infection, with genetic factors is also discussed. It is hoped that understanding the genetic basis for familial gastric cancer will facilitate the development of clinically useful screening and preventative procedures.