E-Selectin S128R Polymorphism is Associated with Cancer Risk: a Meta-analysis

  • Cheng, Da-Ye (Department of Transfusion, The First Hospital of China Medical University) ;
  • Hao, Yi-Wen (Department of Transfusion, The First Hospital of China Medical University) ;
  • Zhou, Wen-Ling (Department of Transfusion, The First Hospital of China Medical University) ;
  • Ma, Yi-Ran (Department of Transfusion, The First Hospital of China Medical University)
  • Published : 2014.04.01


Background: Genetic factors have been shown to play an important role in the development of cancers. However, individual studies may fail to completely demonstrate complicated genetic relationships because of small sample size. Therefore, we performed a meta-analysis to evaluate the association of E-selectin Ser128Arg (S128R) with cancer risk. Materials and Methods: A literature search in PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure databases was carried out to identify studies of the association between E-selectin S128R polymorphism and cancer risk. The odds ratio (OR) with 95% confidence intervals (95%CIs) were used to assess the strength of association. Results: A total of eight studies involving 1,675 cancer cases and 2,285 controls were included in the meta-analysis. In overall populations, S128R polymorphism seemed to be associated with cancer risk (Arg allele vs Ser allele: OR=1.65, 95%CI =1.33-2.04, p<0.01; Arg/Arg+Arg/Ser vs Ser/Ser: OR=1.87, 95%CI =1.48-2.36, p<0.01; Arg/Ser vs Ser/Ser: OR=1.80, 95%CI =1.51-2.14, p<0.01). Similarly, subgroup analysis by ethnicity and source of control also revealed that this polymorphism was related to cancer risk. Conclusions: Our meta-analysis revealed that there was association between the E-selectin S128R polymorphism and the risk of cancer. Further large and well-designed studies are needed to confirm this association.




Supported by : National Natural Science Foundation of China


  1. Xia HZ, Du WD, Wu Q, et al (2012). E-selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population. Mol Carcinog, 51, 597-607.
  2. Zhang YY, Chen B, Ding YQ (2012). Metastasis-associated factors facilitating the progression of colorectal cancer. Asian Pac J Cancer Prev, 13, 2437-44.
  3. Panoussopoulos GS, Theodoropoulos G, Michalopoulos NV, et al (2010). Analysis of E-Selectin S128R gene polymorphism in pancreatic cancer. J Surg Oncol, 102, 604-7.
  4. Ley K (2003). The role of selectins in inflammation and disease. Trends Mol Med, 9, 263-8.
  5. Liarmakopoulos E, Gazouli M, Aravantinos G, et al (2013). E-Selectin S128R gene polymorphism in gastric cancer. Int J Biol Markers, 28, 38-42.
  6. Naidu R, Har YC, Taib NA (2011). Polymorphic variant Ser128Arg of E-Selectin is associated with breast cancer risk and high grade tumors. Onkologie, 34, 592-7.
  7. Porquet N, Poirier A, Houle F, et al (2011). Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFkappaB survival axis downstream of Death receptor-3. BMC Cancer, 11, 285.
  8. Revelle BM, Scott D, Beck PJ (1996). Single amino acid residues in the E- and P-selectin epidermal growth factor domains can determine carbohydrate binding specificity. J Biol Chem, 271, 16160-70.
  9. Sawada R, Tsuboi S, Fukuda M (1994). Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials. J Biol Chem, 269, 1425-31.
  10. Tang L, Xiong T, Jia Q, et al (2014). Study on the association between the Arg194Trp polymorphism in the XRCC1 gene and the risk of hematological malignancies. Tumour Biol, 35, 3009-16.
  11. Wenzel K, Hanke R, Speer A (1994). Polymorphism in the human E-selectin gene detected by PCR-SSCP. Hum Genet, 94, 452-3.
  12. Wermuth N, Cochran WG (1979). Detecting systematic errors in multi-clinic observational data. Biometrics, 35, 683-6.
  13. Ke JJ, Shao QS, Ling ZQ (2006). Expression of E-selectin, integrin beta1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance. World J Gastroenterol, 12, 3609-11.
  14. Hebbar M, Adenis A, Revillion F, et al (2009). E-selectin gene S128R polymorphism is associated with poor prognosis in patients with stage II or III colorectal cancer. Eur J Cancer, 45, 1871-6.
  15. Houlston RS, Peto J (2004). The search for low-penetrance cancer susceptibility alleles. Oncogene, 23, 6471-6.
  16. Jia LQ, Shen YC, Guo SJ, et al (2013). The 2518 A/G polymorphism in the MCP-1 gene and cancer risk: a meta-analysis. Asian Pac J Cancer Prev, 14, 3575-9.
  17. Khatib AM, Fallavollita L, Wancewicz EV, et al (2002). Inhibition of hepatic endothelial E-selectin expression by C-raf antisense oligonucleotides blocks colorectal carcinoma liver metastasis. Cancer Res, 62, 5393-8.
  18. Kontogianni P, Zambirinis CP, Theodoropoulos G, et al (2013). The impact of the stromal cell-derived factor-1-3' A and E-selectin S128R polymorphisms on breast cancer. Mol Biol Rep, 40, 43-50.
  19. Krause T, Turner GA (1999). Are selectins involved in metastasis? Clin Exp Metastasis, 17, 183-92.
  20. Laferriere J, Houle F, Taher MM, et al (2001). Transendothelial migration of colon carcinoma cells requires expression of E-selectin by endothelial cells and activation of stress-activated protein kinase-2 (SAPK2/p38) in the tumor cells. J Biol Chem, 276, 33762-72.
  21. Laubli H, Borsig L (2010). Selectins promote tumor metastasis. Semin Cancer Biol, 20, 169-77.
  22. Laubli H, Spanaus KS, Borsig L (2009). Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes. Blood, 114, 4583-91.
  23. Bevilacqua MP, Nelson RM (1993). Selectins. J Clin Invest, 91, 379-87.
  24. Banks RE, Gearing AJ, Hemingway IK, et al (1993). Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies. Br J Cancer, 68, 122-4.
  25. Barthel SR, Gavino JD, Descheny L, et al (2007). Targeting selectins and selectin ligands in inflammation and cancer. Expert Opin Ther Targets, 11, 1473-91.
  26. Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088-101.
  27. Bond GL, Hu W, Levine A (2005). A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res, 65, 5481-4.
  28. Cheng D, Hao Y, Zhou W, et al (2013). Positive association between Interleukin-8 -251A> T polymorphism and susceptibility to gastric carcinogenesis: a meta-analysis. Cancer Cell Int, 13, 100.
  29. Cummings RD, Smith DF (1992). The selectin family of carbohydrate-binding proteins: structure and importance of carbohydrate ligands for cell adhesion. Bioessays, 14, 849-56.
  30. Da LS, Zhang Y, Zhang S, et al (2013). Association between MCP-1 -2518A/G Polymorphism and Cancer Risk: Evidence from 19 Case-Control Studies. PLoS One, 8, 82855.
  31. Dymicka-Piekarska V, Kemona H (2009). Does colorectal cancer clinical advancement affect adhesion molecules (sP-selectin, sE-selectin and ICAM-1) concentration? Thromb Res, 124, 80-3.
  32. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34.
  33. Bal N, Kocer NE, Ertorer ME, et al (2008). Maspin, E-selectin, and P-selectin expressions in papillary thyroid carcinomas and their correlation with prognostic parameters. Pathol Res Pract, 204, 743-50.
  34. Alessandro R, Seidita G, Flugy AM, et al (2007). Role of S128R polymorphism of E-selectin in colon metastasis formation. Int J Cancer, 121, 528-35.
  35. Alexiou D, Karayiannakis AJ, Syrigos KN, et al (2003). Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients. Am J Gastroenterol, 98, 478-85.
  36. Bai Y (2009). Vascular invasion and eNOS, ICAM-1, E- selectin Polymorphism in oral cancer (Wuhan University).

Cited by

  1. Association of E-selectin S128R polymorphism with hereditary breast carcinoma susceptibility in Turkish patients without BRCA1/2 germline mutations vol.21, pp.1, 2018,