Analysis of E-Selectin S128R gene polymorphism in pancreatic cancer
George S. Panoussopoulos MD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorCorresponding Author
George Theodoropoulos MD, PhD, FACS
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
7 Semitelou Street, GR-11528 Athens, Greece. Fax: +30-2107707574.Search for more papers by this authorNikolaos V. Michalopoulos MD, PhD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorMaria Gazouli PhD
Department of Biology, School of Medicine, University of Athens, Athens, Greece
Search for more papers by this authorJohn Flessas MD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorStela Taka MSc
Department of Biology, School of Medicine, University of Athens, Athens, Greece
Search for more papers by this authorParaskevas Stamopoulos MD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorAndreas Manouras MD, PhD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorGeorge C. Zografos MD, PhD, FACS
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorGeorge S. Panoussopoulos MD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorCorresponding Author
George Theodoropoulos MD, PhD, FACS
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
7 Semitelou Street, GR-11528 Athens, Greece. Fax: +30-2107707574.Search for more papers by this authorNikolaos V. Michalopoulos MD, PhD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorMaria Gazouli PhD
Department of Biology, School of Medicine, University of Athens, Athens, Greece
Search for more papers by this authorJohn Flessas MD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorStela Taka MSc
Department of Biology, School of Medicine, University of Athens, Athens, Greece
Search for more papers by this authorParaskevas Stamopoulos MD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorAndreas Manouras MD, PhD
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorGeorge C. Zografos MD, PhD, FACS
First Propaedeutic Surgical Department, Hippocration University Hospital, University of Athens, Athens, Greece
Search for more papers by this authorAbstract
Background
E-selectin, an intercellular adhesion molecule that plays important roles in metastasis of tumor cells, has a polymorphism in exon 4 that results in the substitution of a serine by an arginine within the extracellular domain of the receptor, which increases its affinity for ligands. No evidence exist on the role of E-selectin polymorphism in pancreatic cancer.
Methods
Eighty pancreatic cancer patients and 160 cases of normal healthy control subjects were investigated for genotype and allelic frequencies of S128R polymorphism of E-selectin gene by PCR–RFLPs.
Results
The frequencies for “AA,” “CA,” and “CC” genotypes were 46.25%, 50%, and 3.75% in patients, and 63.75%, 26.9%, and 9.4% in healthy subjects, respectively. The “C” carriers group of patients (“CA + CC” genotype) and the “C” allele were over-represented among the pancreatic cancer cases (P = 0.012 and 0.096, respectively). Advanced T stage, the presence of lymph node and other adverse pathologic characteristics were not significantly correlated with either the “CA + CC” genotype group of patients or the presence of “C” allele.
Conclusions
E-selectin S128R “C” allele may confer an increased susceptibility to pancreatic cancer development, while its carriage status does not appear to be related to the aggressive features of this malignancy. J. Surg. Oncol. 2010;102:604–607. © 2010 Wiley-Liss, Inc.
REFERENCES
- 1 Evans DB, Lee JE, Pisters PW, et al.: Advances in the diagnosis and treatment of adenocarcinoma of the pancreas. Cancer Treat Res 1997; 90: 109–125.
- 2 Jemal A, Siegel R, Ward E, et al.: Cancer statistics, 2007. CA Cancer J Clin 2007; 57: 43–66.
- 3 Vitone LJ, Greenhalf W, McFaul CD, et al.: The inherited genetics of pancreatic cancer and prospects for secondary screening. Best Pract Res Clin Gastroenterol 2006; 20: 253–283.
- 4 Chambers AF, Groom AC, MacDonald IC: Metastasis: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002; 2: 563–572.
- 5
Orr FW,
Wang HH,
Lafrenie RM, et al.:
Interactions between cancer cells and the endothelium in metastasis.
J Pathol
2000;
190:
310–329.
10.1002/(SICI)1096-9896(200002)190:3<310::AID-PATH525>3.0.CO;2-P CAS PubMed Web of Science® Google Scholar
- 6 Krause T, Turner G: Are selectins involved in metastasis? Clin Exp Metastasis 1999; 17: 183–192.
- 7 Hebbar M, Revillion F, Louchez MM, et al.: The relationship between concentrations of circulating soluble E-selectin and clinical, biological and pathological features in patients with breast cancer. Clin Cancer Res 1998; 4: 373–380.
- 8 Recchi MA, Hebbar M, Hornez L, et al.: Multiplex reverse transcriptase polymerase chain reaction assessment of sialyltransferases expression in human breast cancer. Cancer Res 1998; 58: 4066–4070.
- 9 Hebbar M, Revillion F, Louchez MM, et al.: Prognostic value of circulating soluble E-selectin in node-negative breast cancer patients. Clin Cancer Res 1999; 5: 1427–1435.
- 10 Yamada N, Chung YS, Takatsuka S, et al.: Increased sialyl Lewis A expression and fucosyltransferase activity with acquisition of a high metastatic capacity in a colon cancer cell line. Br J Cancer 1997; 76: 582–587.
- 11 Thomas SN, Zhu F, Schnaar RL, et al.: Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow. J Biol Chem 2008; 283: 15647–15655.
- 12 Wenzel K, Hanke R, Speer A: Polymorphism in the human E-selectin gene detected by PCR–SSCP. Hum Genet 1994; 94: 452–453.
- 13 Revelle BM, Scott D, Beck PJ: Single amino acid residues in the E- and P selectin epidermal growth factor domains can determine carbohydrate binding specificity. J Biol Chem 1996; 271: 16160–16170.
- 14 Rao RM, Clarke JL, Ortlepp S, et al.: The S128R polymorphism of E-selectin mediates neuraminidase-resistant tethering of myeloid cells under shear flow. Eur J Immunol 2002; 32: 251–260.
- 15 Rao RM, Haskard DO, Landis RC: Enhanced recruitment of Th2 and CLA-negative lymphocytes by the S128R polymorphism of E-selectin. J Immunol 2002; 169: 5860–5865.
- 16 Yoshida M, Takano Y, Sasaoka T, et al.: E-selectin polymorphism associated with myocardial infarction causes enhanced leukocyte-endothelial interactions under flow conditions. Arterioscler Thromb Vasc Biol 2003; 23: 783–788.
- 17 Wenzel K, Felix S, Kleber FX, et al.: E-selectin polymorphism and atherosclerosis: An association study. Hum Mol Genet 1994; 3: 1935–1937.
- 18 Auer J, Weber T, Berent R, et al.: Genetic polymorphisms in cytokine and adhesion molecule genes in coronary artery disease. Am J Pharmacogenomics 2003; 3: 317–328.
- 19 Vora DK, Rosenbloom CL, Beaudet AL, et al.: Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster. Genomics 1994; 21: 473.
- 20 Zheng F, Chevalier JA, Zhang LQ, et al.: An HphI polymorphism in the E selectin gene is associated with premature coronary artery. Clin Genet 2001; 59: 58.
- 21 Ye SQ, Usher D, Virgil D, et al.: A Pst I polymorphism detects the mutation of serine 128 to arginine in CD 62E gene- a risk factor for coronary heart disease. J Biomed Sci 1999; 6: 18.
- 22 Bannan S, Mansfield MW, Grant PJ: Soluble vascular cell adhesion molecule-1 and E-selectin levels in relation to vascular risk factors and to E-selectin genotype in the first degree relatives of NIDDM and in NIDDM patients. Diabetologia 1998; 41: 460.
- 23 Hattori H, Sato H, Ito D, et al.: A561C polymorphism of E-selectin is associated with ischemic cerebrovascular disease in the Japanese population without diabetes mellitus and hypercholesterolemia. Brain Res 2006; 1108: 221–223.
- 24 Jilma B, Marsik C, Kovar F, et al.: The single nucleotide polymorphism Ser128Arg in the E-selectin gene is associated with enhanced coagulation during human endotoxemia. Blood 2005; 105: 2380–2383.
- 25 Marasini B, Casari S, Zeni S, et al.: E-selectin polymorphism in autoiimune diseases. Arthritis Rheum 1999; 42: S324.
- 26 Alessandro R, Seidita G, Flugy AM, et al.: Role of S128R polymorphism of E-selectin in colon metastasis formation. Int J Cancer 2007; 121: 528–535.
- 27 Hebbar M, Adenis A, Revillion F, et al.: E-selectin gene S128R polymorphism is associated with poor prognosis in patients with stage II or III colorectal cancer. Eur J Cancer 2009; 45: 1871–1876.
- 28 Houlston R, Tomlinson I: Polymorphisms and colorectal tumor risk. Gastroenterology 2001; 121: 282–301.
- 29 Sawada R, Tsuboi S, Fukuda M: Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials. J Biol Chem 1994; 269: 1425–1431.
- 30
Al-Mehdi AB,
Tozawa K,
Fisher AB, et al.:
Intravascular origin of metastasis from the proliferation of endothelium attached tumor cells: A new model for metastasis.
Nat Med
2000;
6:
100–102.
10.1038/71429 Google Scholar
- 31 Wong C, Song C, Grimes M, et al.: Intravascular location of breast cancer cells after spontaneous metastasis to the lung. Am J Pathol 2002; 161: 749–753.
- 32 Wells A: Tumor invasion: Role of growth factor-induced cell motility. Adv Cancer Res 2000; 78: 31–101.
- 33 Kumar P, Hosaka S, Koch A: Soluble E-selectin induces monocyte chemotaxis through Src family tyrosine kinases. J Biol Chem 2001; 276: 21039–21045.