AUTHOR=Lin Xiao-Hua , Chen Da-Jun , Wang Li-Juan , Wan Xiu-Ping 

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1618597

DOI=10.3389/fgene.2025.1618597

ISSN=1664-8021

ABSTRACT=BackgroundGenetic 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).MethodsA 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.ResultsA 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.ConclusionThis meta-analysis provides strong evidence that the PSCA rs2976392 AA genotype significantly increases susceptibility to gastric cancer, particularly among Asians.