Skip to main content
SpringerLink
Log in

MMP 9 Gene Promoter Polymorphism in Gastric Cancer

  • Original Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Matrix metalloproteinase-9 (gelatinase B) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C) > thymidine (T) single nucleotide polymorphism (SNP) at position −1562 in the MMP-9 promoter is reported to influence the expression of the gene. Genotyping of MMP-9 −1562 C→T promoter polymorphism in 140 gastric cancer patients and 132 healthy control subjects was carried out in order to evaluate its association with progression and development of gastric cancer. The SNP was genotyped by tetra-primer amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. Statistical methods were adopted to test for the significance of the results. Risk factor profile of the patients revealed age above 50 years, smoking, alcoholism as the factors associated with the disease. The distribution of genotype frequencies in gastric cancer patients were 28.7 % of CC, 45.5 % of CT and 25.7 % of TT, whereas in control subjects 31.8 % of CC, 53.03 % of CT and 15.15 % of TT, respectively. The allelic frequencies were 51.51 % of C and 48.48 % of T in patient group and 58.33 % of C and 41.66 % of T in controls respectively. The present study shows the possible association of epidemiological risk factors with gastric cancer. There is an increased frequency of T allele in the disease compared to control subjects. However, there is no association of the MMP-9 −1562 C→T promoter polymorphism in the development of gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lauren CCR, Evely CFS, da Diana Mendes F, Mariana FL, Adriana CG, Danielle QC. Interrelationship between MYC gene numerical aberrations and protein expression in individuals from northern Brazil with early gastric adenocarcinoma. Cancer Genet Cytogenet. 2008;181(1):31–5.

    Article  Google Scholar 

  2. Schwartz G. Invasion and metastasis in gastric cancer: in vitro and in vivo models with clinical considerations. Semin Oncol. 1996;23:316–24.

    PubMed  CAS  Google Scholar 

  3. Neugut AI, Hayek M, Howe G. Epidemiology of gastric cancer. Semin Oncol. 1996;23:281–91.

    PubMed  CAS  Google Scholar 

  4. Sun HK, Tae EJ, Ji UK, Kye CK, Jong WP, Seung MN. Prognostic implications for gastric carcinoma based on loss of heterozygosity genotypes correlation with clinicopathologic variables. Cancer Genet Cytogenet. 2004;153:26–31.

    Article  Google Scholar 

  5. Folgueras AR, Pendas AM, Sanchez LM, Lopez-Otin C. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol. 2004;48:411–24.

    Article  PubMed  CAS  Google Scholar 

  6. Hibbs MS, Hoidal JR, Kang AHJ. Expression of a metalloproteinase that degrades native type V collagen and denatured collagens by cultured human alveolar macrophages. Clin Invest. 1987;80:1644–50.

    Article  CAS  Google Scholar 

  7. Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA, Goldberg GI. SV40-transformed human lung fibroblasts secrete a 92 kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem. 1989;264:17213–21.

    PubMed  CAS  Google Scholar 

  8. Murphy G, Ward R, Hembry RM, Reynolds JJ, Kuhn K, Tryggvason K. Characterization of gelatinase from pig polymorphonuclear leucocytes. A metalloproteinase resembling tumour type IV collagenase. Biochem J. 1989;258:463–72.

    PubMed  CAS  Google Scholar 

  9. Senior RM, Griffin GL, Fliszar CJ, Shapiro SD, Goldberg GI, Welgus HG. Human 92- and 72-kilodalton type IV collagenases are elastases. J Biol Chem. 1991;266:7870–5.

    PubMed  CAS  Google Scholar 

  10. Welgus HG, Campbell EJ, Cury JD, Eisen AZ, Senior RM, Wilhelm SM, et al. Neutral metalloproteinases produced by human mononuclear phagocytes. Enzyme profile, regulation, and expression during cellular development. J Clin Invest. 1990;86:1496–502.

    Article  PubMed  CAS  Google Scholar 

  11. Campbell EJ, Cury JD, Shapiro SD, Goldberg GI, Welgus HG. Neutral proteinases of human mononuclear phagocytes: cellular differentiation markedly alters cell phenotype for serine proteinases, metalloproteinases, and TIMP. J Immunol. 1991;146:1286–93.

    PubMed  CAS  Google Scholar 

  12. Watanabe H, Nakanishi I, Yamashita K, Hayakawa T. OkadaY. Matrix metalloproteinase-9 (92 kDa gelatinase/type IV collagenase) from U937 monoblastoid cells: correlation with cellular invasion. J Cell Sci. 1993;104:991–9.

    PubMed  CAS  Google Scholar 

  13. O-charoenrat P, Rhys-Evans PH, Eccles SA. Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 2001;127:813–20.

    PubMed  CAS  Google Scholar 

  14. Folgueras AR, Pendas AM, Sanchez LM, Lopez-Otin C. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol. 2004;48:411–24.

    Article  PubMed  CAS  Google Scholar 

  15. Vaira D, Holton J, Cains S, Polydorou A, Falzon M, Dowsett J, et al. Urease test for Campylobacter pylori: care in interpretation. J Clin Pathol. 1988;41:812–3.

    Article  PubMed  CAS  Google Scholar 

  16. Lahiri DK, Nurnberger JI Jr. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1992;19(19):5444.

    Article  Google Scholar 

  17. Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods Mol Biol. 2009;472:467–77.

    Article  PubMed  Google Scholar 

  18. Baiping Z, Shu Y, de Moniek M, Alun E, et al. Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation. 1999;99:1788–94.

    Article  Google Scholar 

  19. Sugimoto M, Yoshida S, Kennedy S, Deguchi M, Ohara N, Maruo T. Matrix metalloproteinase-1 and -9 promoter polymorphisms and endometrial carcinoma risk in a Japanese population. J Soc Gynecol Invest. 2006;13(7):523–9.

    CAS  Google Scholar 

  20. Matsumura S, Oue N, Nakayama H, Kitadai Y, Yoshida K, Yamaguchi Y, et al. A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer. J Cancer Res Clin. 2005;131(1):19–25.

    Article  CAS  Google Scholar 

  21. Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  22. Sung NY, Choi KS, Park ES, Park K, Lee SY, Lee AK, et al. Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study. Br J Cancer. 2007;97:700–4.

    Article  PubMed  CAS  Google Scholar 

  23. Matsuhashi T, Yamada N, Shinzawa H, Takahashi T. Effect of alcohol on tumor growth of hepatocellular carcinoma with type C cirrhosis. Intern Med. 1996;35(6):443–8.

    Article  PubMed  CAS  Google Scholar 

  24. Tan W, Bailey AP, Shparago M, Busby B, Covington J, Johnson JW, et al. Chronic alcohol consumption stimulates VEGF expression, tumor angiogenesis and progression of melanoma in mice. Cancer Biol Ther. 2007;6(8):1211–7.

    Article  PubMed  CAS  Google Scholar 

  25. Zhao W, Liu H, Xu S, Entschladen F, Niggemann B, Zanker KS, et al. Migration and metalloproteinases determine the invasive potential of mouse melanoma cells, but not melanin and telomerase. Cancer Lett. 2001;162(Suppl):S49–55.

    Article  PubMed  CAS  Google Scholar 

  26. Bodey B, Bodey B Jr, Siegel SE, Kaiser HE. Matrix metalloproteinase expression in malignant melanomas: tumor-extracellular matrix interactions in invasion and metastasis. In Vivo. 2001;15(1):57–64.

    PubMed  CAS  Google Scholar 

  27. Hofmann UB, Eggert AA, Blass K, Brocker EB, Becker JC. Expression of matrix metalloproteinases in the micro environment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation. Cancer Res. 2003;63(23):8221–5.

    PubMed  CAS  Google Scholar 

  28. Matsumura S, Oue N, Nakayama H, et al. A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer. J Cancer Res Clin. 2005;131(1):19–25.

    Article  CAS  Google Scholar 

  29. Kubben FJGM, Sier CFM, Meijer MJW, van den Berg M, van der Reijden JJ, Griffioen G, et al. Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer. Br J Cancer. 2006;95:744–51.

    Article  PubMed  CAS  Google Scholar 

  30. Zhang X, Miao X, Xiong P, et al. Matrix metalloproteinase (MMP-2 and -9 functional single nucleotide polymorphism and gastric cancer. Cancer. 2004;23(11):1233–7.

    CAS  Google Scholar 

Download references

Acknowledgments

Financial support, from Department of Biotechnology (DBT), New Delhi is acknowledged.

Author information

Authors and Affiliations

  1. Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500 016, India

    D. Krishnaveni, Amar Chand Bhayal, K. Sri Manjari, A. Jyothy & A. Venkateshwari

  2. Department of Gastroenterology, Gandhi Hospital, Hyderabad, 500 003, India

    A. Vidyasagar, M. Uma Devi & M. Ramanna

  3. Department of Genetics, Osmania University, Hyderabad, 500 007, India

    Pratibha Nallari

Authors
  1. D. Krishnaveni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amar Chand Bhayal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Sri Manjari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Vidyasagar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Uma Devi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Ramanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Jyothy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pratibha Nallari
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Venkateshwari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Venkateshwari.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krishnaveni, D., Bhayal, A.C., Sri Manjari, K. et al. MMP 9 Gene Promoter Polymorphism in Gastric Cancer. Ind J Clin Biochem 27, 259–264 (2012). https://doi.org/10.1007/s12291-012-0210-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-012-0210-2

Keywords

Search

Navigation