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.
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)).
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.
These results indicated that the rs2294008 pol</span>ymorphism of PSCA gene may play a role in bladdercancer carcinogenesis and it could be served as a biomarker for genetic susceptibility to bladder cancer in Chinese populations.
Overall, seven of the 14 variants were significantly associated with bladder cancer risk (p = 9.763 × 10(-3) for rs9642880 at 8q24.21, p = 3.004 × 10(-3) for rs2294008 at 8q24.3, p = 0.012 for rs798766 at 4p16.3, p = 0.034 for rs1495741 at 8p22, p = 2.306 × 10(-4) for GSTM1, p = 8.507 × 10(-8) for rs17674580 at 18q12.3, p = 7.179 × 10(-4) for rs10936599 at 3q26.2) and the odds ratios (ORs) ranged from 1.13 to 1.65.
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).
Cumulative evidence of an association was graded as strong for rs2294008 [odds ratio (OR) = 1.32, P = 5.1 × 10-33], rs2976392 (OR = 1.29, P = 1.8 × 10-8), rs9297976 (OR = 0.75, P = 1.4 × 10-7), rs2976391 (OR = 1.38, P = 6.1 × 10-5) and rs138377917 (OR = 0.53, P = 0.008) with gastric cancer, rs2294008 with bladder cancer (OR = 1.15, P = 8.0 × 10-19), gastritis (OR = 1.35, P = 1.2 × 10-5), duodenal ulcer (OR = 0.68, P = 2.4 × 10-57) and gastric ulcer (OR = 0.88, P = 1.7 × 10-7).
If validated in further studies, PSCA rs2294008</span> could be useful marker of sur</span>vival assessment and individualized clinical therapy for gastric cancer, particularly among the diffuse-type 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.
Overall, seven of the 14 variants were significantly associated with bladder cancer risk (p = 9.763 × 10(-3) for rs9642880 at 8q24.21, p = 3.004 × 10(-3) for rs2294008 at 8q24.3, p = 0.012 for rs798766 at 4p16.3, p = 0.034 for rs1495741 at 8p22, p = 2.306 × 10(-4) for GSTM1, p = 8.507 × 10(-8) for rs17674580 at 18q12.3, p = 7.179 × 10(-4) for rs10936599 at 3q26.2) and the odds ratios (ORs) ranged from 1.13 to 1.65.
The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008.
The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008.
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.
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.
Based on the statistical evidence, we can draw a conclusion that the rs2294008 polymorphism of PSCA gene is likely to play a role in cancer carcinogenesis, especially in gastric cancer and bladder cancer.
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.
Although modest limitations and potential bias cannot be eliminated, this meta-analysis suggests that PSCA -rs2294008C>T and -rs2976392G>A are potential factors of GC development for Eastern Asians, and future work may incorporate these findings and evaluate these variants as potential markers for screening and early diagnosis of GC.
In conclusion, The T allele of PSCA rs2294008 is associated with increased risk of gastric cancer, especially intestinal type, poorly differentiated, early onset, and noncardia gastric cancer in Chinese population.