A new study in Nature Genetics shows that a version of a SNP in a gene called PSCA is associated with an increased risk in Asians for diffuse-type gastric cancer, a type of stomach cancer.
Gastric cancer, which falls into two main categories — intestinal and diffuse — is the fourth most common type of cancer and second leading cause of cancer death worldwide.
The intestinal type of gastric cancer is typically associated with infection by a type of bacteria called H. pylori, while the diffuse type is not. Previous research suggests that the two types of gastric cancer develop through different pathways and that genetic background is more important for the diffuse type.
Millennium Genome Project
The Study Group of Millennium Genome Project for Cancer initially examined more than 85,000 SNPs in 188 diffuse-type gastric cancer patients and 752 healthy controls from Japan to find DNA variations that might be associated with diffuse-type gastric cancer. That research produced a list of 2,880 candidate SNPs that were then examined in an additional 749 patients and 750 controls.
The SNP from that shorter list that was most strongly associated with diffuse-type gastric cancer was rs2976392, in the PSCA gene.
Because the SNPs that are found in genome-wide association studies are often only markers for other SNPs that are actually affecting susceptibility to a disease, the researchers looked at the PSCA gene more closely to find additional SNPs.
PSCA SNP rs2294008 was found to be significantly associated with diffuse-type gastric cancer. Each copy of the T version (which is the most common version in the Japanese population) increased the odds of diffuse-type gastric cancer by 1.67 times.
Association in Koreans
The researchers found that rs2294008 was also associated with diffuse-type gastric cancer in a Korean sample of 454 patients and 390 controls. In this population the T version increased the odds of diffuse-type gastric cancer by 1.91 times. In the Korean population, the T version is less common than the C version of SNP rs2294008.
The researchers think the different versions of rs2294008 might influence the risk for diffuse-type gastric cancer because theory predicts the T and C versions of this SNP should produce slightly different proteins. Laboratory experiments also suggested that when the PSCA gene has the T version of rs2294008, less protein is made from the gene.
More research will be needed to confirm that the T version of rs2294008 is a risk factor for diffuse-type gastric cancer in Asian populations and if so, how it works. Researchers will also need to determine whether this SNP is associated with diffuse-type gastric cancer in other populations.
