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A full genome scan for gastric cancer

It is generally accepted that multiple factors play a role in gastric carcinogenesis, including diet,1,2 lifestyle,3 infectious agents such as Helicobacter pylori ( H. pylori ),4,5 and genetic factors as well as gene-environment interactions.6,7 Although the continuous decrease in the incidence of gastric cancer in recent decades can be explained by changing lifestyle, diet habits, and reduced H. pylori infection, the fact that some individuals develop gastric cancer while others do not under similar environmental exposures suggests that genetic predisposition plays an important role in the pathogenesis of this disease. In addition, familial clustering of cases of gastric cancer, a higher incidence of the disease among the relatives of patients than among matched controls, and a more common coincidence of the disease in homozygotic than in heterozygotic twins, also supports genetic links with gastric cancer.8,9,10

In contrast with the vast amount of accumulated information on environmental factors, little is known about the genetic factors linked to gastric cancer. Several studies have reported disease susceptible loci for gastric cancer, based on association analysis of candidate genes involved in DNA repair, detoxification, or the immune system.11 Studies on familial clustering of gastric cancer revealed germline mutations in CDH1, ATM, and MET.12–14 In addition, gastric cancer frequently occurs in family members with monogenic diseases such as hereditary non-polyposis colorectal cancer, Li-Fraumeni syndrome, familial adenomatous polyposis, and Peutz-Jeghers syndrome.15–18 However, these polymorphisms and/or mutations cannot explain the overall genetic components of gastric cancer.

It is now feasible to screen the entire human genome for genes exerting a major effect on susceptibility to multifactorial diseases. Because gastric cancer, like many complex diseases, exhibits genetic heterogeneity, we carried out a genome-wide linkage study to search for possible susceptibility loci related to gastric …