Association of the PSCA rs2294008 C>T Polymorphism with Gastric Cancer Risk: Evidence from a Meta-Analysis

  • Zhang, Qing-Hui ;
  • Yao, Yong-Liang ;
  • Gu, Tao ;
  • Gu, Jin-Hua ;
  • Chen, Ling ;
  • Liu, Yun
  • Published : 2012.06.30


Background: Multiple studies have reported associations between the PSCA rs2294008 C > T polymorphism and GC, but susceptibility has proven inconsistent. Therefore, we estimates the relationship between the rs2294008 C > T polymorphism and GC by meta-analysis. Methods: PubMed, Embase and Web of Science databases were searched and nine independent case-control studies were included in this meta-analysis. Crude ORs with 95% CIs were extracted according to the Mantal-Haenszel method and pooled to assess the strength of the association. Results: We observed that the PSCA rs2294008 C > T polymorphism was significantly correlated with GC risk when all studies were pooled into the meta-analysis. Further subgroup analysis showed the polymorphism to be linked with diffuse and noncardia GC in the allele contrast model, homozygote codominant model, dominant model, and recessive model. However, no connection was apparent for intestinal and cardia GC. In the stratified analysis by ethnicity, significant associations were observed in Asians for the recessive model. Interestingly, the relationship was particularly significant in the Chinese population. Conclusions: Our findings suggest that the PSCA rs2294008 C > T polymorphism is a risk factor for GC, especially in diffuse and noncardia GC and in Chinese.


Prostate stem-cell antigen;gastric cancer;genetic polymorphisms;risk


  1. Argani P, Rosty C, Reiter RE, et al (2001). Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma. Cancer Res, 11, 4320-4.
  2. Bahrenberg G, Brauers A, Joost HG, et al (2000). Reduced expression of PSCA, a member of the LY-6 family of cell surface antigens, in bladder, esophagus, and stomach tumors. Biochem Biophys Res Commun, 3, 783-8.
  3. Dong LM, Potter JD, White E, et al (2008). Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA, 20, 2423-36.
  4. Elsamman E, Fukumori T, Kasai T, et al (2006). Prostate stem cell antigen predicts tumour recurrence in superficial transitional cell carcinoma of the urinary bladder. BJU Int, 6, 1202-7.
  5. Elsamman EM, Fukumori T, Tanimoto S, et al (2006). The expression of prostate stem cell antigen in human clear cell renal cell carcinoma: a quantitative reverse transcriptasepolymerase chain reaction analysis. BJU Int, 3, 668-73.
  6. Feng HC, Tsao SW, Nqan HY, et al (2008). Overexpression of prostate stem cell antigen is associated with gestational trophoblastic neoplasia. Histopathology, 2, 167-74.
  7. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 12, 2893-917.
  8. Grubbs EG, Abdel-Wahab Z, Tyler DS, et al (2006). Utilizing quantitative polymerase chain reaction to evaluate prostate stem cell antigen as a tumor marker in pancreatic cancer. Ann Surg Oncol, 12, 1645-54.
  9. Jose S, George PS, Mathew A (2008). Assessment of confounding and interaction using the mantel-haenszel risk estimation method. Asian Pac J Cancer Prev, 2, 323-5.
  10. Kamangar F, Dawsey SM, Blaser MJ, et al (2006). Opposing risks of gastric cardia and noncardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity. J Natl Cancer Inst, 20, 1445-52.
  11. Kjellsson MC, Zingmark PH, Jonsson EN, et al (2008). Comparison of proportional and differential odds models for mixed-effects analysis of categorical data. J Pharmacokinet Pharmacodyn, 5, 483-501.
  12. Lao-Sirieix P, Caldas C, Fitzgerald RC (2010). Genetic predisposition to gastro-oesophageal cancer. Curr Opin Genet Dev, 3, 210-7.
  13. Lochhead P, Frank B, Hold GL, et al (2011). Genetic variation in the prostate stem cell antigen gene and upper gastrointestinal cancer in white individuals. Gastroenterology, 2, 435-41.
  14. Lu Y, Chen J, Ding Y, et al (2010). Genetic variation of PSCA gene is associated with the risk of both diffuse- and intestinaltype gastric cancer in a Chinese population. Int J Cancer, 9, 2183-9.
  15. Matsuo K, Tajima K, Suzuki T, et al (2009). Association of prostate stem cell antigen gene polymorphisms with the risk of stomach cancer in Japanese. Int J Cancer, 8, 1961-4.
  16. Ou J, Li K, Ren H, et al (2010). Association and haplotype analysis of prostate stem cell antigen with gastric cancer in Tibetans. DNA Cell Biol, 6, 319-23.
  17. Reiter RE, Gu Z, Watabe T, et al (1998). Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci U S A, 4, 1735-40.
  18. Sakamoto H, Yoshimura K, Saeki N, et al (2008). Genetic variation in PSCA is associated with susceptibility to diffusetype gastric cancer. Nat Genet, 6, 730-40.
  19. Sala N, Muñoz X, Travier N, et al (2012). Prostate stem-cell antigen gene is associated with diffuse and intestinal gastric cancer in Caucasians: Results from the EPIC-EURGAST study. Int J Cancer, 10, 2417-27.
  20. Shi Y, Hu Z, Wu C, et al (2011). A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. Nat Genet, 12, 1215-8.
  21. Song HR, Kim HN, Piao JM, et al (2011). Association of a common genetic variant in prostate stem-cell antigen with gastric cancer susceptibility in a Korean population. Mol Carcinog, 11, 871-5.
  22. Tan VP, Wong BC (2011). Helicobacter pylori and gastritis: Untangling a complex relationship 27 years on. J Gastroenterol Hepatol, Suppl 1, 42-5.
  23. Wu C, Wang G, Yang M, et al (2009). Two genetic variants in prostate stem cell antigen and gastric cancer susceptibility in a Chinese population. Mol Carcinog, 12, 1131-8.
  24. Zeng Z, Wu X, Chen F, et al (2011). Polymorphisms in prostate stem cell antigen gene rs2294008 increase gastric cancer risk in Chinese. Mol Carcinog, 5, 353-8.

Cited by

  1. Genetic Variation in PSCA and Risk of Gastric Advanced Preneoplastic Lesions and Cancer in Relation to Helicobacter pylori Infection vol.8, pp.9, 2013,
  2. Associations of Genetic Variants in the PSCA, MUC1 and PLCE1 Genes with Stomach Cancer Susceptibility in a Chinese Population vol.10, pp.2, 2015,
  3. PSCA rs2294008 Polymorphism with Increased Risk of Cancer vol.10, pp.8, 2015,
  4. Genetic variation and gastric cancer risk: a field synopsis and meta-analysis vol.64, pp.8, 2015,
  5. Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population vol.7, pp.2, 2016,