Association between functional PSMD10 Rs111638916 variant regulated by MiR-505 and gastric cancer risk in a Chinese population.

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.