Meng Wang,1,* Xi-Jing Wang,1,* Yun-Feng Ma,2,* Xiao-Bin Ma,1 Zhi-Ming Dai,3 Ye Lv,1 Shuai Lin,1 Xing-Han Liu,1 Peng-Tao Yang,1 Zhi-Jun Dai1,4 1Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Immunology and Pathogenic Biology, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Center for Translational Medicine, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China *These authors contributed equally to this work Background: Previous studies suggested genetic variations in PSCA (prostate stem cell antigen) may confer the susceptibility of cancer. Many case–control studies have reported the relationship between PSCA rs2294008 C > T polymorphism and cancer, especially gastric cancer and bladder cancer. However, the results are inconsistent. This meta-analysis is aimed at evaluating the association of rs2294008 polymorphism with cancer risk. Methods: The databases of PubMed, ISI Web of Knowledge, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for related publications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Fixed models were used when heterogeneity among studies was not detected, otherwise the random model was used. Results: Twenty-six studies from 24 articles with 30,050 multiple cancer cases and 51,670 controls were pooled into this meta-analysis. The results showed that the rs2294008 polymorphism was associated with increased cancer risk in any genetic model (T vs C, OR: 1.18, 95% CI: 1.08–1.28; TT vs CC, OR: 1.36, 95% CI: 1.14–1.62; TC vs CC, OR: 1.29, 95% CI: 1.17–1.44; TT + TC vs CC, OR: 1.32, 95% CI: 1.18–1.49; TT vs TC + CC, OR: 1.15, 95% CI: 1.02–1.30). In stratified analysis by cancer type, we found that the T allele had a significant high risk of gastric and bladder cancer, but not in other cancers. In subgroup analysis by ethnicity, increased cancer risk was found in both Asians and Caucasians. Conclusion: Our study suggested that the PSCA rs2294008 C > T polymorphism is a risk factor for cancer, especially in gastric and bladder cancer. Keywords: risk, meta-analysis, prostate stem cell antigen, single nucleotide polymorphisms, SNPs