| Theme |
Risk Factors and Prevention of Gastric Cancer |
| Title |
Genome-wide Association Study of Gastric Cancer and Disease Genome Database |
| Author |
Norihisa Saeki |
Genetics Division, National Cancer Center Research Institute |
| Author |
Hiromi Sakamoto |
Genetics Division, National Cancer Center Research Institute |
| Author |
Teruhiko Yoshida |
Genetics Division, National Cancer Center Research Institute |
| [ Summary ] |
A JSNP-based genome-wide association study was conducted on diffuse-type gastric cancer in Japan to reveal the possibility of the PSCA gene as a novel genetic susceptibility factor. The association was clearly significant with diffuse-type, but not so in intestinal-type, gastric cancer. Importantly, the association was replicated in an independent Korean case-control panel. PSCA expression was apparently localized in the gastric mucosal region, where epithebal stem cells and precursors are considered to be present. Moreover, PSCA was down-regulated in gastric cancer tissues, and its products exhibited cell-growth inhibitory activity in vitro. A functional SNP was identified by the reporter assay, which indicated that the risk allele suppressed a promoter activity of the PSCA gene. These findings suggest that the PSCA gene contributes to gastric carcinogenesis through the cell-growth regulation of gastric epithelial precursors. Summary statistics for the genome scan has been published from a disease genome database, GeMDBJ (http://gemdbj.nibio.go.jp/). |