E-Cadherin Germline Mutations and Risk of Gastric Cancer

patients with a strong family history of gastric cancer were largely confined to these subjects with evidence of current or previous H. pylori infection. This is consistent with the genetic abnormality making them particularly prone to develop gastric cancer if infected with H. pylori, but not necessarily increasing the risk of cancer in the absence of the infection. Consequently, it is very important to know whether the patients with the E-cadherin mutations who went on to develop gastric cancer had evidence of current or previous H. pylori infection. It is also important to know the state of the noncancerous gastric mucosa from which these tumors have arisen. It is curious to note that diffuse gastric cancers are the most common tumors in families with E-cadherin germline mutations. H. pylori infection, the commonest chronic bacterial infection in the world, may act as the trigger to the disordered epithelial tissue polarity and structural integrity that characterize E-cadherin deficiency. It is also now recognized that proximal cardia cancers have a different etiological basis from the more distal gastric cancers, with H. pylori infection being a strong risk factor for the latter but not the former.5 Indeed, there is some evidence that H. pylori infection may be protective against cardia cancer.6 It is therefore also important to know the location of the cancers that developed in the patients with the E-cadherin mutations and, in particular, to know whether it is a risk factor for cardia cancer. If the germline mutations only increase the risk of noncardia gastric cancer, this would suggest that H. pylori infection is an important cofactor. Recommending prophylactic gastrectomy in a currently healthy individual is an unenviable task and it must be based on the most reliable information regarding the risk of cancer for that particular individual. We suspect that the recorded high incidence of gastric cancer in patients with the E-cadherin germline mutations is likely to be influenced by the previous high background prevalence of H. pylori infection.