Recently, two genome-wide association studies identified a significant association between the prostate stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and risk of diffuse-type of gastric cancer in Asians and bladder cancer in Caucasians, respectively.
Genetic variations of prostate stem cell antigen (PSCA) contribute to the risk of gastric cancer for Eastern Asians: a meta-analysis based on 16792 individuals.
Recently, three genome-wide association studies have identified the PSCA (prostate stem cell antigen) rs2294008 polymorphism (C > T) associated with susceptibility to gastric cancer, bladder cancer, and duodenal ulcers, highlighting its critical role in disease pathogenesis.
A genome-wide study performed in a Japanese population identified a strong association between SNP rs2294008 (Met1Thr) in the Prostate Stem Cell Antigen gene (PSCA) and diffuse-type gastric cancer (GC).
Our findings demonstrated that rs2294008 and rs2976392 polymorphism of PSCA is a risk-conferring factor associated with increased GC susceptibility, especially in East Asians.
In previous work, we found that prostate stem cell antigen (PSCA) gene, encoding a glycosylphosphatidylinositol-anchored protein, is a presumable tumor suppressor in gastric cancer and gallbladder cancer (GBC).
We conducted a systematic review and meta-analysis for relevant literatures to quantitatively evaluate the relationship between PSCA polymorphisms and GC susceptibility.
We found that the T allele of rs2294008, an intronic variant of the PSCA gene at 8q24 that was previously associated with an increased risk of gastric cancer, was inversely associated with a decreased risk of ESCC (odds ratio = 0.90; 95% confidence interval, 0.81-0.99; P = 0.034).
In conclusion, the results indicated that the PSCArs2294008 T and rs2976392 A alleles were low-penetrate risk factors for GCa in this study population.
From these results we conclude that the PSCArs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.
Large meta-analyses confirmed the association between IL8, IL10, TNF-b, TP53 and PSCA, while genetic variation at different genes such as XPG, PLCE1, HFE, ERCC5, EZH2, DOC2, CYP19A1, ALDH2, and CDH1 have been reported to be associated with GC risk.
For PSCArs2294008 C > T polymorphism, there was a significantly increased risk of gastric cancer in all genetic models (TT/TC vs. CC: OR = 1.61, 95 % CI = 1.35-1.91; TT vs.
In conclusion, The T allele of PSCArs2294008 is associated with increased risk of gastric cancer, especially intestinal type, poorly differentiated, early onset, and noncardia gastric cancer in Chinese population.
Many epidemiological studies have identified the PSCArs2294008 T-allele as a risk factor of GC, while others have found an association between the rs2294008 C-allele and risk of DU and gastric ulcer (GU).
These findings imply that the T allele significantly suppresses PSCA expression in vivo by recruiting YY1 to its promoter, which eventually predisposes gastric epithelial cells to GC development.