BACKGROUND/AIMS: Gankyrin is an oncoprotein involved in regulating the cell cycle through protein-protein interactions with cyclin-dependent kinase 4 and p53. However, its association with gastric cancer (GC) risk has not yet been determined. In this study, we investigated micro RNA (miRNA)-associated single nucleotide polymorphisms (SNPs) in the 3'-untranslated region (UTR) of the gankyrin gene PSMD10 to clarify the relationship between these SNPs and miRNAs in Chinese patients with GC. METHODS: We performed a case-control study including 857 GC patients and 748 cancer-free controls. PSMD10 expression was investigated using genotyping, real-time polymerase chain reaction, cell transfection, and dual luciferase reporter assays. RESULTS: Patients with histories of smoking, alcohol consumption, and cancer were more susceptible to GC than controls. The SNP rs111638916 in the PSMD10 3'-UTR was identified as a risk factor for GC and acted as a tumor promoting factor. SNP rs111638916 was also regulated by miR-505, resulting in up-regulation of gankyrin expression in patients with GA and AA genotypes. Carriers of the GA and AA genotypes also presented with larger tumors and had a higher risk of metastasis. CONCLUSION: The PSMD10 rs111638916 SNP is highly associated with an increased risk of GC in Chinese patients, and could serve as a novel biomarker for this disease.
BACKGROUND/AIMS: Gankyrin is an oncoprotein involved in regulating the cell cycle through protein-protein interactions with cyclin-dependent kinase 4 and p53. However, its association with gastric cancer (GC) risk has not yet been determined. In this study, we investigated micro RNA (miRNA)-associated single nucleotide polymorphisms (SNPs) in the 3'-untranslated region (UTR) of the gankyrin gene PSMD10 to clarify the relationship between these SNPs and miRNAs in Chinese patients with GC. METHODS: We performed a case-control study including 857 GC patients and 748 cancer-free controls. PSMD10 expression was investigated using genotyping, real-time polymerase chain reaction, cell transfection, and dual luciferase reporter assays. RESULTS:Patients with histories of smoking, alcohol consumption, and cancer were more susceptible to GC than controls. The SNP rs111638916 in the PSMD10 3'-UTR was identified as a risk factor for GC and acted as a tumor promoting factor. SNP rs111638916 was also regulated by miR-505, resulting in up-regulation of gankyrin expression in patients with GA and AA genotypes. Carriers of the GA and AA genotypes also presented with larger tumors and had a higher risk of metastasis. CONCLUSION: The PSMD10rs111638916 SNP is highly associated with an increased risk of GC in Chinese patients, and could serve as a novel biomarker for this disease.