Genetic Variation in PSCA is Associated with Bladder Cancer Susceptibility in a Korean Population

  • Lee, Jun-Ho ;
  • Song, Hye-Rim ;
  • Kim, Hee Nam ;
  • Kweon, Sun-Seog ;
  • Yun, Yong-Woon ;
  • Choi, Jin-Su ;
  • Jung, Seung-Il ;
  • Kwon, Dong Deuk ;
  • Kim, Soo Hyun ;
  • Choi, Yoo-Duk ;
  • Shin, Min-Ho
  • Published : 2014.11.06


Background: Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population. Materials and Methods: We conducted a case-control study of 411 bladder cancer patients and 1,700 controls. Results: The frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were 16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in controls, respectively. We found that the combined CT/TT genotypes were associated with a significantly increased risk of bladder cancer (OR CT/TT =1.58, 95% CI= 1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and tumor stage did not modify the association between rs2294008 and the risk of bladder cancer. Conclusions: Our study showed that the rs2294008 polymorphism in the PSCA gene is associated with the risk of bladder cancer in a Korean population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity.


PSCA;bladder cancer;SNP;ethnicity


  1. Dudek AM, Grotenhuis AJ, Vermeulen SH, et al (2013). Urinary bladder cancer susceptibility markers. what do we know about functional mechanisms? Int J Mol Sci, 14, 12346-66.
  2. Fu YP, Kohaar I, Rothman N, et al (2012). Common genetic variants in the PSCA gene influence gene expression and bladder cancer risk. Proc Natl Acad Sci USA, 109, 4974-9.
  3. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  4. Kiemeney LA, Sulem P, Besenbacher S, et al (2010). A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nat Genet, 42, 415-9.
  5. Rafnar T, Vermeulen SH, Sulem P, et al (2011). European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene. Hum Mol Genet, 20, 4268-81.
  6. Kiemeney LA, Thorlacius S, Sulem P, et al (2008). Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat Genet, 40, 1307-12.
  7. Kiriluk KJ, Prasad SM, Patel AR, et al (2012). Bladder cancer risk from occupational and environmental exposures. Urol Oncol, 30, 199-211.
  8. Ma Z, Hu Q, Chen Z, et al (2013). Systematic evaluation of bladder cancer risk-associated single-nucleotide polymorphisms in a chinese population. Mol Carcinog, 52, 916-21.
  9. Rothman N, Garcia-Closas M, Chatterjee N, et al (2010). A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nat Genet, 42, 978-84.
  10. Saeki N, Gu J, Yoshida T, et al (2010). Prostate stem cell antigen: a Jekyll and Hyde molecule? Clin Cancer Res, 16, 3533-8.
  11. Sakamoto H, Yoshimura K, Saeki N, et al (2008). Genetic variation in PSCA is associated with susceptibility to diffusetype gastric cancer. Nat Genet, 40, 730-40.
  12. 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, 50, 871-5.
  13. The Korea Central Cancer Registry NCC (2012). Annual report of cancer statistics in Korea in 2010. Ministry of Health and Welfare.
  14. Volanis D, Kadiyska T, Galanis A, et al (2010). Environmental factors and genetic susceptibility promote urinary bladder cancer. Toxicol Lett, 193, 131-7.
  15. Wang T, Zhang L, Li H, et al (2012). Prostate stem cell antigen polymorphisms and susceptibility to gastric cancer: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev, 21, 843-50.
  16. Wallerand H, Bakkar AA, de Medina SG, et al (2005). Mutations in TP53, but not FGFR3, in urothelial cell carcinoma of the bladder are influenced by smoking: contribution of exogenous versus endogenous carcinogens. Carcinogenesis, 26, 177-84.
  17. Wang P, Ye D, Guo J, et al (2014). Genetic score of multiple riskassociated single nucleotide polymorphisms is a marker for genetic susceptibility to bladder cancer. Genes Chromosomes Cancer, 53, 98-105.
  18. Wang S, Tang J, Wang M, et al (2010). Genetic variation in PSCA and bladder cancer susceptibility in a Chinese population. Carcinogenesis, 31, 621-4.
  19. Wu X, Ye Y, Kiemeney LA, et al (2009). Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. Nat Genet, 41, 991-5.
  20. Wu XR (2005). Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer, 5, 713-25.
  21. Zeegers MP, Tan FE, Dorant E, et al (2000). The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies. Cancer, 89, 630-9.<630::AID-CNCR19>3.0.CO;2-Q

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