The Association Between the Survivin C-31G Polymorphism and Gastric Cancer Risk in a Chinese Population

  • Li Yang
  • Huaijun Zhu
  • Bo Zhou
  • Haijuan Gu
  • Hongli Yan
  • Naping Tang
  • Hanzhang Dong
  • Qingmin Sun
  • Rihong Cong
  • Guoyu Chen
  • Bin Wang
Original Article


Introduction The C-31G polymorphism in the survivin promoter could de-represse the cell-cycle-dependent transcription of the human survivin gene, resulting in overexpression of survivin. This survivin mutation has only been studied on cervical carcinoma. However, no study has ever been conducted to evaluate the effect of the polymorphism on other cancers, including gastric cancer. Methods In this hospital-based, case–control study, we investigated the association between the survivin C-31G polymorphism and risk of gastric cancer in a Chinese population using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) protocols. Results No statistically significant association was observed between gastric cancer risk and the variant genotype (GG + GC). However, the variant genotype (GG + GC) was either associated with risk of distal gastric cancer (odds ratios = 0.50, 95% confidence interval = 0.30–0.83) or with risk of well-differentiated tumor (odds ratios = 0.46, 95% confidence interval = 0.22–0.97). Conclusion Our results demonstrate that the survivin C-31G polymorphism may be involved in distal gastric carcinogenesis and tumor differentiation in a Chinese population.


Survivin Polymorphism Gastric cancer Apoptosis 



Confidence interval


Odds ratio


Polymerase chain reaction


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106–130.PubMedCrossRefGoogle Scholar
  3. 3.
    He J, Gu D, Wu X, et al. Major causes of death among men, women in China. N Engl J Med. 2005;353:1124–1134. doi:10.1056/NEJMsa050467.PubMedCrossRefGoogle Scholar
  4. 4.
    Wu MS, Chen CJ, Lin JT. Host–environment interactions: their impact on progression from gastric inflammation to carcinogenesis and on development of new approaches to prevent and treat gastric cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1878–1882. doi:10.1158/1055-9965.EPI-04-0792.PubMedCrossRefGoogle Scholar
  5. 5.
    Roberts-Thomson IC, Butler WJ. Polymorphism and gastric cancer. J Gastroenterol Hepatol. 2005;20:793–794. doi:10.1111/j.1440-1746.2005.03938.x.PubMedCrossRefGoogle Scholar
  6. 6.
    Zhu H, Yang L, Zhou B, Yu R, Tang N, Wang B. Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case–control study. Carcinogenesis. 2006;27:2491–2496. doi:10.1093/carcin/bgl121.PubMedCrossRefGoogle Scholar
  7. 7.
    Johnson ME, Howerth EW. Survivin: a bifunctional inhibitor of apoptosis protein. Vet Pathol. 2004;41:599–607. doi:10.1354/vp.41-6-599.PubMedCrossRefGoogle Scholar
  8. 8.
    Li F, Brattain MG. Role of the Survivin gene in pathophysiology. Am J Pathol. 2006;169:1–11. doi:10.2353/ajpath.2006.060121.PubMedCrossRefGoogle Scholar
  9. 9.
    Fukuda S, Pelus LM. Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther. 2006;5:1087–1098. doi:10.1158/1535-7163.MCT-05-0375.PubMedCrossRefGoogle Scholar
  10. 10.
    Chiou SK, Moon WS, Jones MK, Tarnawski AS. Survivin expression in the stomach: implications for mucosal integrity and protection. Biochem Biophys Res Commun. 2003;305:374–379. doi:10.1016/S0006-291X(03)00724-1.PubMedCrossRefGoogle Scholar
  11. 11.
    Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–921. doi:10.1038/nm0897-917 PubMedCrossRefGoogle Scholar
  12. 12.
    Li F. Survivin study: what is the next wave. J Cell Physiol. 2003;197:8–29. doi:10.1002/jcp. 10327.PubMedCrossRefGoogle Scholar
  13. 13.
    Ikeguchi M, Kaibara N. Changes in survivin messenger RNA level during cisplatin treatment in gastric cancer. Int J Mol Med. 2001;8:661–666.PubMedGoogle Scholar
  14. 14.
    Rödel F, Hoffmann J, Distel L, et al. Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res. 2005;65:4881–4887. doi:10.1158/0008-5472.CAN-04-3028.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhang B, Liu JY, Pan JS, et al. Combined treatment of ionizing radiation with genistein on cervical cancer HeLa cells. J Pharmacol Sci. 2006;102:129–135. doi:10.1254/jphs.FP0060165.PubMedCrossRefGoogle Scholar
  16. 16.
    Zhang B, Pan JS, Liu JY, Han SP, Hu G, Wang B. Effects of chemotherapy and/or radiotherapy on survivin expression in ovarian cancer. Methods Find Exp Clin Pharmacol. 2006;28:619–625. doi:10.1358/mf.2006.28.9.1003581.PubMedCrossRefGoogle Scholar
  17. 17.
    Lu CD, Altieri DC, Tanigawa N. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res. 1998;58:1808–1812.PubMedGoogle Scholar
  18. 18.
    Zhu XD, Lin GJ, Qian LP, Chen ZQ. Expression of survivin in human gastric carcinoma and gastric carcinoma model of rats. World J Gastroenterol. 2003;9:1435–1438.PubMedGoogle Scholar
  19. 19.
    Yu J, Leung WK, Ebert MP, et al. Increased expression of survivin in gastric cancer patients and in first degree relatives. Br J Cancer. 2002;87:91–97. doi:10.1038/sj.bjc.6600421.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang ZN, Xu HM, Jiang L, Zhou X, Lu C, Zhang X. Expression of survivin in primary and metastatic gastric cancer cells obtained by laser capture microdissection. World J Gastroenterol. 2004;10:3094–3098.PubMedGoogle Scholar
  21. 21.
    Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by surviving. Nature. 1998;396:580–584. doi:10.1038/25141.PubMedCrossRefGoogle Scholar
  22. 22.
    Otaki M, Hatano M, Kobayashi K, Ogasawara T, Kuriyama T, Tokuhisa T. Cell cycle-dependent regulation of TIAP/m-survivin expression. Biochim Biophys Acta. 2000;1493:188–194.PubMedGoogle Scholar
  23. 23.
    Li F, Altieri DC. The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression. Cancer Res. 1999;59:3143–3151.PubMedGoogle Scholar
  24. 24.
    Xu Y, Fang F, Ludewig G, Jones G, Jones D. A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells. DNA Cell Biol. 2004;23:419–429. doi:10.1089/1044549041474788.PubMedCrossRefGoogle Scholar
  25. 25.
    Borbély AA, Murvai M, Szarka K, et al. Survivin promoter polymorphism and cervical carcinogenesis. J Clin Pathol. 2007;60:303–306. doi:10.1136/jcp. 2006.037804.PubMedCrossRefGoogle Scholar
  26. 26.
    Reed JC. The Survivin saga goes in vivo. J Clin Invest. 2001;108:965–969. doi:10.1172/JCI14123.PubMedCrossRefGoogle Scholar
  27. 27.
    Miyachi K, Sasaki K, Onodera S, et al. Correlation between survivin mRNA expression and lymph node metastasis in gastric cancer. Gastric Cancer. 2003;6:217–224. doi:10.1007/s10120-003-0255-2.PubMedCrossRefGoogle Scholar
  28. 28.
    Kania J, Konturek SJ, Marlicz K, Hahn EG, Konturek PC. Expression of survivin and caspase-3 in gastric cancer. Dig Dis Sci. 2003;48:266–271. doi:10.1023/A:1021915124064.PubMedCrossRefGoogle Scholar
  29. 29.
    Tu SP, Jiang XH, Lin MC, et al. Suppression of survivin expression inhibits in vivo tumorigenicity and angiogenesis in gastric cancer. Cancer Res. 2003;63:7724–7732.PubMedGoogle Scholar
  30. 30.
    Chiou SK, Tanigawa T, Akahoshi T, Abdelkarim B, Jones MK, Tarnawski AS. Survivin: a novel target for indomethacin-induced gastric injury. Gastroenterology. 2005;128:63–73. doi:10.1053/j.gastro.2004.10.008.PubMedCrossRefGoogle Scholar
  31. 31.
    Meng H, Lu C, Mabuchi H, Tanigawa N. Prognostic significance and different properties of survivin splicing variants in gastric cancer. Cancer Lett. 2004;216:147–155. doi:10.1016/j.canlet.2003.12.020.PubMedCrossRefGoogle Scholar
  32. 32.
    Yang LQ, Fang DC, Wang RQ, Yang SM. Effect of NF-kappaB, survivin, Bcl–2 and Caspase3 on apoptosis of gastric cancer cells induced by tumor necrosis factor related apoptosis inducing ligand. World J Gastroenterol. 2004;10:22–25.PubMedGoogle Scholar
  33. 33.
    Ikeguchi M, Liu J, Kaibara N. Expression of survivin mRNA and protein in gastric cancer cell line (MKN-45) during cisplatin treatment. Apoptosis. 2002;7:23–29. doi:10.1023/A:1013556727182.PubMedCrossRefGoogle Scholar
  34. 34.
    Nakamura M, Tsuji N, Asanuma K, et al. Survivin as a predictor of cis-diamminedichloroplatinum sensitivity in gastric cancer patients. Cancer Sci. 2004;95:44–51. doi:10.1111/j.1349-7006.2004.tb03169.x.PubMedCrossRefGoogle Scholar
  35. 35.
    Wakana Y, Kasuya K, Katayanagi S, et al. Effect of survivin on cell proliferation and apoptosis in gastric cancer. Oncol Rep. 2002;9:1213–1218.PubMedGoogle Scholar
  36. 36.
    Koyama S. Differential expression of intracellular apoptotic signaling molecules in tumor and tumor-infiltrating lymphocytes during development of invasion and/or metastasis of gastric carcinoma. Dig Dis Sci. 2003;48:2290–2300. doi:10.1023/B:DDAS.0000007865.96569.9a.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Li Yang
    • 1
  • Huaijun Zhu
    • 2
  • Bo Zhou
    • 3
  • Haijuan Gu
    • 3
  • Hongli Yan
    • 4
  • Naping Tang
    • 3
  • Hanzhang Dong
    • 1
  • Qingmin Sun
    • 3
  • Rihong Cong
    • 3
  • Guoyu Chen
    • 1
  • Bin Wang
    • 3
  1. 1.Department of General SurgeryFirst Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of PharmacyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
  3. 3.Department of Pharmacology, Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjingChina
  4. 4.Dongzhi Health Inspection BureauDongzhiChina

Personalised recommendations