Diagnosis and treatment for familial gastric cancer

The criteria for familial gastric cancer are as follows: 1) there should be at least 3 relatives with gastric cancer, 2) one should be a first-degree relative of the other 2, 3) at least 2 successive generations should be affected, 4) at least 1 should be diagnosed before age 50, and 5) other familial tumors should be excluded. There are two types of familial gastric cancer, diffuse type and intestinal type, of which the genetic background seems to be differ. In 1998, an autosomal dominant syndrome of diffuse gastric cancer was reported with germline mutations in the E-cadherin gene and has been identified in approximately 14 families and 50 individuals worldwide. In addition, an inherited mutation in mismatch repair (MMR) genes was found in hereditary non-polyposis colorectal cancer (HNPCC) in 1993. Since there is high frequency microsatellite instability found in familial gastric cancer patients, vigorous efforts have been made to find abnormalities in MMR genes of familial gastric cancer patients. However, to date, there has been little progress in detecting MMR gene mutations in familial gastric cancer patients. It is clinically most important to obtain a detailed family history to identify familial gastric cancer patients. At present, prophylactic total gastrectomy for familial gastric cancer is under careful consideration.