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The functional polymorphism in monocyte chemoattractant protein-1 gene increases susceptibility to gastric cancer

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Abstract

Monocyte chemoattractant protein-1 (MCP-1, CCL2) has been suggested to be associated with gastric cancer. We investigated whether the functional single nucleotide polymorphism A-2518G in CCL2 gene influenced susceptibility to gastric cancer. The CCL2 genotypes were determined using polymerase chain reaction–restriction fragment length polymorphism in 1,216 individuals (608 gastric cancer patients and 608 age- and sex-matched controls). The gastric cancer patients showed a significant higher frequency of the variant G allele compared to the controls (P = 0.01). Compared with the wild-type AA carriers, the variant genotypes (GA + GG) of A-2518G polymorphism were associated with a higher risk of gastric cancer (adjusted odds ratio = 1.55, 95% confidence interval = 1.03–2.35). Moreover, the elevated risk of gastric cancer associated with the variant genotypes was especially noteworthy in rural subjects (adjusted odds ratio = 1.92, 95% confidence interval = 1.01–3.65). In addition, stratification of gastric cancer cases according to clinicopathological characters showed that the polymorphism was associated significantly with the depth of tumor infiltration. Our data suggest that the genetic polymorphism CCL2 A-2518G may not only be associated with an increased risk of gastric cancer, but also with advanced stage of gastric cancer in the Chinese population.

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References

  1. Rollins BJ, Walz A, Baggiolini M. Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes. Blood. 1991;78:1112–6.

    PubMed  CAS  Google Scholar 

  2. Lu B, et al. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med. 1998;187:601–8.

    Article  PubMed  CAS  Google Scholar 

  3. Conti I, Rollins BJ. CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol. 2004;14:149–54.

    Article  PubMed  CAS  Google Scholar 

  4. Salcedo R, et al. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood. 2000;96:34–40.

    PubMed  CAS  Google Scholar 

  5. Craig MJ, Loberg RD. CCL2 (Monocyte Chemoattractant Protein-1) in cancer bone metastases. Cancer Metastasis Rev. 2006;25:611–9.

    Article  PubMed  CAS  Google Scholar 

  6. Kuroda T, et al. Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment. Clin Cancer Res. 2005;11:7629–36.

    Article  PubMed  CAS  Google Scholar 

  7. Ohta M, et al. Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human gastric carcinomas. Int J Oncol. 2003;22:773–8.

    PubMed  CAS  Google Scholar 

  8. Rovin BH, Lu L, Saxena R. A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun. 1999;259:344–8.

    Article  PubMed  CAS  Google Scholar 

  9. Gu H, et al. Gly82Ser Polymorphism of the Receptor for Advanced Glycation End Products Is Associated with an Increased Risk of Gastric Cancer in a Chinese Population. Clin Cancer Res. 2008;14:3627–32.

    Article  PubMed  CAS  Google Scholar 

  10. Zhu HJ, Yang L, Zhou B, et al. Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case-control study. Carcinogenesis. 2006;27:2491–6.

    Article  PubMed  CAS  Google Scholar 

  11. Gu HJ, et al. Association of endothelin-converting enzyme-1b C-338A polymorphism with gastric cancer risk: a case–control study. Eur J Cancer. 2008;44:1253–8.

    Article  PubMed  CAS  Google Scholar 

  12. Yang L, et al. Tissue inhibitor of metalloproteinase-2 G-418C polymorphism is associated with an increased risk of gastric cancer in a Chinese population. Eur J Surg Oncol. 2008;34:636–41.

    Article  PubMed  CAS  Google Scholar 

  13. Attar R, et al. Association of CCL2 and CCR2 gene variants with endometrial cancer in Turkish women. In Vivo. 2010;24:243–8.

    PubMed  CAS  Google Scholar 

  14. Ghilardi G, et al. Breast cancer progression and host polymorphisms in the chemokine system: role of the macrophage chemoattractant protein-1 (MCP-1) -2518 G allele. Clin Chem. 2005;51:452–5.

    Article  PubMed  CAS  Google Scholar 

  15. Tse KP, et al. MCP-1 Promoter Polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment. Clin Cancer Res. 2007;13:6320–6.

    Article  PubMed  CAS  Google Scholar 

  16. Sobin LH, Wittekind CH, editors. TNM classification of malignant tumors. 5th ed. New York: Wiley & Sons, Inc; 1997. p. 59–62.

    Google Scholar 

  17. Li S, et al. MCP-1 overexpressed in tuberous sclerosis lesions acts as a paracrine factor for tumor development. J Exp Med. 2005;202:617–24.

    Article  PubMed  CAS  Google Scholar 

  18. Saji H, et al. Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer. 2001;92:1085–91.

    Article  PubMed  CAS  Google Scholar 

  19. Loberg RD, et al. CCL2 is a potent regulator of prostate cancer cell migration and proliferation. Neoplasia. 2006;8:578–86.

    Article  PubMed  CAS  Google Scholar 

  20. Futagami S, et al. Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer. J Gastroenterol. 2008;43:216–24.

    Article  PubMed  CAS  Google Scholar 

  21. Watanabe T, et al. Monocyte chemotactic protein-1 regulates leukocyte recruitment during gastric ulcer recurrence induced by tumor necrosis factor-alpha. Am J Physiol Gastrointest Liver Physiol. 2004;287:G919–28.

    Article  PubMed  CAS  Google Scholar 

  22. Isomoto H, et al. Mucosal concentrations of proinflammatory cytokines and chemokines at gastric cardia: implication of Helicobacter pylori infection and gastroesophageal reflux. Am J Gastroenterol. 2004;99:1063–8.

    Article  PubMed  CAS  Google Scholar 

  23. Flores-Villanueva PO, et al. A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis. J Exp Med. 2005;202:1649–58.

    Article  PubMed  CAS  Google Scholar 

  24. Cho ML, et al. The MCP-1 promoter -2518 polymorphism in Behcet’s disease: correlation between allele types, MCP-1 production and clinical symptoms among Korean patients. Autoimmunity. 2004;37:77–80.

    Article  PubMed  CAS  Google Scholar 

  25. Hung RJ, et al. Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk. Carcinogenesis. 2004;25:973–8.

    Article  PubMed  CAS  Google Scholar 

  26. Polonikov AV, et al. A common polymorphism G-50T in cytochrome P450 2J2 gene is associated with increased risk of essential hypertension in a Russian population. Dis. Markers. 2008;24:119–26.

    CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 30672486).

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Pharmacy, Nantong Tumor Hospital, 226361, Nantong, Jiangsu, China

    Haijuan Gu, Meixin Ni, Xiaohong Guo, Ping Feng, Yanyan Xu & Xiang Gu

  2. Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu, China

    Li Yang

  3. Department of Pharmacology, Nanjing Medical University, 210029, Nanjing, Jiangsu, China

    Bin Wang

Authors
  1. Haijuan Gu
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  2. Meixin Ni
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  3. Xiaohong Guo
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  4. Ping Feng
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  5. Yanyan Xu
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  6. Xiang Gu
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  7. Li Yang
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  8. Bin Wang
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Corresponding author

Correspondence to Haijuan Gu.

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Haijuan Gu and Meixin Ni contributed equally to this work.

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Gu, H., Ni, M., Guo, X. et al. The functional polymorphism in monocyte chemoattractant protein-1 gene increases susceptibility to gastric cancer. Med Oncol 28 (Suppl 1), 280–285 (2011). https://doi.org/10.1007/s12032-010-9748-0

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  • DOI: https://doi.org/10.1007/s12032-010-9748-0

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