Many epidemiological studies have identified the PSCA rs2294008 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).
We found that both rs2294008 (CT vs. CC, OR = 1.55, 95% CI = 1.20-1.99, <i>P</i><0.001 and CT+TT vs. CC, OR = 1.38, 95% CI = 1.09-1.74, <i>P</i>=0.008) and rs2976392 (GA vs. GG, OR = 1.61, 95% CI = 1.25-2.07, <i>P</i><0.001 and GA+AA vs. GG, OR = 1.52, 95% CI = 1.20-1.92, <i>P</i><0.001) were associated with an increased gastric cancer.
We conducted a case-control association study of <i>H. pylori</i>-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (<i>P =</i> 9.4 × 10<sup>-5</sup>; odds ratio = 3.88, TT + TC vs CC genotype), but not with <i>H. pylori</i> infection <i>per se</i> nor with the progression from active gastritis to gastric cancer.
However, subtype-specific associations were observed for gastric cardia adenocarcinomas at MUC1/TRIM46/1q22 rs2070803 [HRAA versus GA+GG = 2.16; 95% confidence interval (CI) = 1.24-3.78; P = 0.0068] and LTA/TNF/6p21.33 rs1799724 (HRTT+CT versus CC = 1.30; 95% CI = 1.07-1.57; P = 0.0077), and for diffuse-type GC at PSCA/8q24.3 rs2294008 (HRTT versus CT+CC = 1.99; 95% CI = 1.33-2.97; P = 7.8E-04).
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.
In conclusion, the results indicated that the PSCA rs2294008 T and rs2976392 A alleles were low-penetrate risk factors for GCa in this study population.
Previous genomewide association studies identified prostate stem cell antigen (PSCA) as a gastric cancer (GC) susceptibility gene and showed an association between GC and the T allele of the single nucleotide polymorphism rs2294008 (C/T) in this gene.
The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer.
From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.
Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU).
Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07-1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03-1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02-1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00-1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15-1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14-1.84), respectively.
The variant C allele of the reference SNP rs2294008 in the PSCA gene was associated with a significantly reduced risk of GC (per allele-adjusted odds ratio [aOR], 0.51; 95% confidence interval [CI], 0.33-0.77; P = .002).
In addition, our data indicate that rs22</span>94008 of PSCA is involved in GC susceptibility and confer its effect primarily in noncardia tumors (OR = 1.30, 95% CI 1.12-1.53, P < 10(-4)).
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).
The C allele of rs2294008 at PSCA was associated with increased risk of duodenal ulcer (odds ratio (OR) = 1.84; P = 3.92 × 10(-33)) in a recessive model but was associated with decreased risk of gastric cancer (OR = 0.79; P = 6.79 × 10(-12)), as reported previously.
These findings supported that PSCA rs2294008 C > T and rs2976392 G > A polymorphisms may contribute to the susceptibility to gastric cancer, particular in non-cardia or diffused gastric cancer.
These results confirm the association between variation in the promoter region of PSCA and GC risk in Caucasians and also indicate that the rs2294</span>008 variant is a similar risk factor for both the diffuse and intestinal-types of GC.