Association between the PSCA rs2976392 polymorphism and susceptibility to gastric cancer: a meta-analysis

Genetic polymorphisms, such as PSCA rs2976392, have been implicated in gastric carcinogenesis, but it is unclear whether there is a direct association. Thus, we conducted a comprehensive meta-analysis to evaluate the association between the PSCA rs2976392 polymorphism and susceptibility to gastric cancer (GC).

A systematic search of the PubMed, Web of Science, Embase, and Cochrane Library databases was performed up to 13 March 2025. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for five genetic models. Subgroup analyses were conducted according to ethnicity and Hardy-Weinberg equilibrium (HWE) status. Heterogeneity and publication bias were assessed, and sensitivity analyses were performed.

A total of 13 studies involving 9,255 patients with gastric cancer and 8,903 controls were included. Overall, a significant association between the PSCA rs2976392 polymorphism and increased GC risk was observed under the allele model (OR = 1.29, 95% CI: 1.19-1.40), dominant model (OR = 1.53, 95% CI: 1.3-1.77), homozygous model (OR = 1.52, 95% CI: 1.18-1.96), and heterozygous model (OR = 1.52, 95% CI: 1.33-1.73), but not under the recessive model. Subgroup analyses revealed a strong association in Asian populations with all genetic models, whereas Caucasians showed a significant association only with the homozygous model. No significant publication bias was detected, and sensitivity analyses confirmed the robustness of the results.

This meta-analysis provides strong evidence that the PSCA rs2976392 AA genotype significantly increases susceptibility to gastric cancer, particularly among Asians.