Genetic factors related to gastric cancer susceptibility identified using a genome‐wide association study

<jats:p>Gastric cancer (<jats:styled-content style="fixed-case">GC</jats:styled-content>) is one of the major malignant diseases worldwide, especially in <jats:styled-content style="fixed-case">A</jats:styled-content>sia, where <jats:styled-content style="fixed-case">J</jats:styled-content>apan and <jats:styled-content style="fixed-case">K</jats:styled-content>orea have the highest incidence in the world. Gastric cancer is classified into intestinal and diffuse types. While the former is almost absolutely caused by <jats:italic><jats:styled-content style="fixed-case">H</jats:styled-content>elicobacter pylori</jats:italic> infection as the initial insult, the latter seems to include cases in which the role of infection is limited, if any, and a contribution of genetic factors is anticipated. Previously, we performed a genome‐wide association study (<jats:styled-content style="fixed-case">GWAS</jats:styled-content>) on diffuse‐type <jats:styled-content style="fixed-case">GC</jats:styled-content> by using single nucleotide polymorphisms (<jats:styled-content style="fixed-case">SNP</jats:styled-content>) catalogued for Japanese population (<jats:styled-content style="fixed-case">JSNP</jats:styled-content>), and identified a prostate stem cell antigen (<jats:italic><jats:styled-content style="fixed-case">PSCA</jats:styled-content></jats:italic>) gene encoding a glycosylphosphatidylinositol‐anchored cell surface antigen as a <jats:styled-content style="fixed-case">GC</jats:styled-content> susceptibility gene. From the second candidate locus identified using the <jats:styled-content style="fixed-case">GWAS</jats:styled-content>, 1q22, we found the Mucin 1 (<jats:italic><jats:styled-content style="fixed-case">MUC</jats:styled-content>1</jats:italic>) gene encoding a cell membrane‐bound mucin protein as another gene related to diffuse‐type <jats:styled-content style="fixed-case">GC</jats:styled-content>. A two‐allele analysis based on risk genotypes of the two genes revealed approximately 95% of Japanese population have at least one of the two risk genotypes, and approximately 56% of the population have both risk genotypes. The two‐<jats:styled-content style="fixed-case">SNP</jats:styled-content> genotype might offer ample room to further stratify a high <jats:styled-content style="fixed-case">GC</jats:styled-content> risk subpopulation in Japan and Asia by adding another genetic and/or non‐genetic factor. Recently, a <jats:styled-content style="fixed-case">GWAS</jats:styled-content> on the Chinese population disclosed an additional three <jats:styled-content style="fixed-case">GC</jats:styled-content> susceptibility loci: 3q13.31, 5p13.1 and 10q23. (<jats:italic>Cancer Sci</jats:italic> 2013; 104: 1–8)</jats:p>