Our results confirm an association between gastric cancer in Europeans and three loci previously reported in Asians, MUC1, PRKAA1 and PSCA, refine the association signal at PRKAA1 and support a pathogenic role for the tandem repeat identified in MUC1.
The PSCArs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCArs2294008 T allele carriers, but not duodenal ulcer.
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.
Our study showed that rs2294008 in the PSCA gene was associated with increased risks of gastric cancer in a Korean population, suggests that rs2294008 might play an important role in gastric carcinogenesis.
If validated in further studies, PSCArs2294008 could be useful marker of survival assessment and individualized clinical therapy for gastric cancer, particularly among the diffuse-type gastric cancer.
Our study suggested rs2294008 in the PSCA gene to be associated with increased risk of gastric cancer and rs2070803 in MUC1 to play a protective role in a Chinese population.
The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.
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).
Previously, we performed a genome-wide association study (GWAS) on diffuse-type GC by using single nucleotide polymorphisms (SNP) catalogued for Japanese population (JSNP), and identified a prostate stem cell antigen (PSCA) gene encoding a glycosylphosphatidylinositol-anchored cell surface antigen as a GC susceptibility gene.
Recent exciting findings that genetic variations of PSCA conferred increased risks of gastric cancer and bladder cancer have opened up a new avenue of research about the pathological function of PSCA.
Specifically, a significant increased stomach cancer risk was associated with PSCArs2294008 (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), PSCArs2976392 (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.
Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in the PSCA gene were recently identified as the susceptibility loci of gastric cancer, especially in diffuse type.
Rs2294008T was a cis-expression quantitative trait loci for PSCA, upregulating mRNA in normal gastric (β = 0.60; P = 5.7E-21) and GC (β = 0.30; P = 0.0089) tissues.