Overview

Despite a declining incidence of, and mortality from, gastric cancer worldwide, it remains the second largest cause of cancer-related death. Most gastric cancers occur sporadically without evidence of an inherited cancer predisposition. Familial clustering of gastric cancer is observed in approximately 10% of cases. However, hereditary gastric cancer caused by inheritance of germline mutations accounts for only 1-3% of all gastric cancers and is seen in HDGC, hereditary nonpolyposis colon cancer syndrome (HNPCC), Peutz-Jeghers syndrome, Cowden's syndrome, and some kindreds affected with Li-Fraumeni syndrome and familial adenomatous polyposis (FAP; Table 1). Compared with other malignancies such as colorectal cancer, the genetic events that contribute to the tumorigenicity of gastric cancer are rather undefined. However, it is believed that complex interactions between dietary factors, Helicobacter pylori infection, and genetic predisposition contribute to the pathogenesis of gastric cancer, account for phenotypic differences, and explain the increasing age-related pene-trance of tumorigenic phenotype.

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