A single nucleotide polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer

  • Shunji Matsumura
  • Naohide Oue
  • Yasuhiko Kitadai
  • Kazuaki Chayama
  • Kazuhiro Yoshida
  • Yoshiyuki Yamaguchi
  • Tetsuya Toge
  • Kazue Imai
  • Kei Nakachi
  • Wataru Yasui
Original Paper

Abstract

Purpose

Matrix metalloproteinase-1 (MMP-1) plays a key role in cancer invasion and metastasis by degradation of extracellular matrix (ECM) and basement membrane barriers. The 1G/2G single nucleotide polymorphism (SNP) in the MMP-1 promoter at position –1607 bp has been reported to affect the transcriptional activity. In the light of these findings, we investigated whether this SNP in the MMP-1 promoter is associated with the development, differentiation, and progression of gastric cancer.

Methods

The 215 gastric cancer patients and 166 controls were used in this study. The SNP of the MMP-1 promoter was analyzed by PCR-RFLP and sequencing. The genotype frequency was compared between cases and controls, and the association with clinicopathological parameters among cases was studied.

Results

The frequency of 1G/2G genotypes in gastric cancer patients was similar to those in controls (p=0.57). The degree of tumor invasion, the presence of lymph node metastasis, and clinical stage showed no significant association with the SNP. On the other hand, we found a significant association with histological differentiation and gender among gastric cancer patients (p<0.05, respectively).

Conclusions

The presence of 2G allele in the MMP-1 promoter did not enhance the risk of gastric cancer; however, it may be involved in differentiation of gastric cancer.

Keywords

SNP MMP-1 Gastric cancer 

References

  1. Baker EA, Leaper DJ (2003) The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology. Eur J Cancer 39:981–988CrossRefPubMedGoogle Scholar
  2. Chen MJ, Chiou YY, Wu SL (2000) Lifestyle habits and gastric cancer in hospital-based case-control study in Taiwan. Am J Gastroenterol 95:3242–3249CrossRefPubMedGoogle Scholar
  3. Forget MA, Desrosiers RR, Beliveau R (1999) Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis. Can J Physiol Pharmacol 77:465–480CrossRefPubMedGoogle Scholar
  4. Furuya Y, Ichikura T, Mochizuki H (1999) Interleukin-1alpha concentration in tumors as a risk factor for liver metastasis in gastric cancer. Surg Today 29:288–289CrossRefPubMedGoogle Scholar
  5. Ghilardi G, Biondi ML, Mangoni J, Leviti S, DeMonti M, Guagnellini E, Scorza R (2001) Matrix metalloproteinase-1 promoter polymorphism 1G/2G is correlated with colorectal cancer invasiveness. Clin Cancer Res 7:2344–2346PubMedGoogle Scholar
  6. Hewitt RE, Leach IH, Powe DG, Clark IM, Cawston TE, Turner DR (1991) Distribution of collagenase and tissue inhibitor of metalloproteinases (TIMP) in colorectal tumours. Int. J Cancer 49:666–672Google Scholar
  7. Inoue T, Yashiro M, Nishimura S, Maeda K, Sawada T, Ogawa Y, Sowa M, Chung KH (1999) Matrix metalloproteinase-1 expression is a prognostic factor for patients with advanced gastric cancer. Int J Mol Med 4:73–77PubMedGoogle Scholar
  8. Ito R, Kitadai Y, Kyo E, Yokozaki H, Yasui W, Yamashita U, Nikai H, Tahara E (1993) Interleukin 1 alpha acts as an autocrine growth stimulator for human gastric carcinoma cells. Cancer Res 53:4102–4106Google Scholar
  9. Ito T, Ito M, Shiozawa J, Naito S, Kanematsu T, Sekine I (1999) Expression of the MMP-1 in human pancreatic carcinoma: relationship with prognostic factor. Mod Pathol 12:669–674PubMedGoogle Scholar
  10. Japanese Gastric Cancer Association (1998) Japanese Classification of Gastric Carcinoma – 2nd English Edition. Gastric Cancer 1:10–24CrossRefPubMedGoogle Scholar
  11. Kanamori Y, Matsushima M, Minaguchi T, Kobayashi K, Sagae S, Kudo R, Terakawa N, Nakamura Y (1999) Correlation between expression of the matrix metalloproteinase-1 gene in ovarian cancers and an insertion/deletion polymorphism in its promoter region. Cancer Res 59:4225–4227PubMedGoogle Scholar
  12. Kohn EC, Liotta LA (1995) Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res 55:1856–1862PubMedGoogle Scholar
  13. Lauren P (1965) The two histological main types of gastric carcinoma. Diffuse and so-called intestinal type carcinoma: an attempt at histological classification. Acta Pathol Microbiol Scand 64:31–49Google Scholar
  14. Liotta LA, Steeg PS, Stetler Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336PubMedGoogle Scholar
  15. Marbaix E, Donnez J, Courtoy PJ, Eeckhout Y (1992) Progesterone regulates the activity of collagenase and related gelatinases A and B in human endometrial explants. Proc Natl Acad Sci USA 89:11789–11793PubMedGoogle Scholar
  16. McDonnel S, Matrisian LM (1991) Stromelysin in tumor progression and invasion. Cancer Metastasis Rev 9:305–319Google Scholar
  17. Migita T, Sato E, Saito K, Mizoi T, Shiiba K, Matsuno S, Nagura H, Ohtani H (1999) Differing expression of MMPs-1 and –9 and urokinase receptor between diffuse- and intestinal-type gastric carcinoma. Int J Cancer 84:74–79PubMedGoogle Scholar
  18. Murray GI, Duncan ME, Arbuckle E, Melvin WT, Fothergill JE (1998a) Matrix metalloproteinases and their inhibitors in gastric cancer. Gut 43:791–797PubMedGoogle Scholar
  19. Murray GI, Duncan ME, O’Neil P, Mckay JA, Melvin WT, Fothergill JE (1998b) Matrix metalloprotease-1 is associated with poor prognosis in oesophageal cancer. J Pathol 185:256–261CrossRefPubMedGoogle Scholar
  20. Nishioka Y, Kobayashi K, Sagae S, Ishioka S, Nishikawa A, Matsushima M, Kanamori Y, Minaguchi T, Nakamura Y, Tokino T, Kudo R (2000) A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter in endometrial carcinomas. Jpn J Cancer Res 91:612–615PubMedGoogle Scholar
  21. Ochiai A, Yasui W, Tahara E (1985) Growth-promoting effect of gastrin on human gastric carcinoma cell line TMK-1. Jpn J Cancer Res 76:1064–1071PubMedGoogle Scholar
  22. Otani Y, Kubota T, Sakurai Y, Igarashi N, Yokoyama T, Kimata M, Wada N, Kameyama K, Kumai K, Okada Y, Kitajima M (1999) Expression of matrix metalloproteinases in gastric carcinoma and possibility of clinical application of matrix metalloproteinase inhibitor in vivo. Ann N Y Acad Sci 30:541–543Google Scholar
  23. Park CC, Bissell MJ, Barcellos-Hoff MH (2000) The influence of the microenvironment on the malignant phenotype. Mol Med Today 6:324–329CrossRefPubMedGoogle Scholar
  24. Rutter JL, Mitchell TI, Buttice G, Meyers J, Gusella JF, Ozelius LJ, Brinckerhoff CE (1998) A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res 58:321–5325Google Scholar
  25. Schneikert J, Peterziel H, Defossez PA, Klocker H, Launoit Y, Cato ACB (1996) Androgen receptor-Ets protein interaction is a novel mechanism for steroid hormone-mediated down-modulation of matrix metalloproteinase expression. J Biol Chem 271:23907–23913PubMedGoogle Scholar
  26. Singer CF, Marbaix E, Kokorine I, Lemoine P, Donnez J, Eeckhout Y, Courtoy PJ (1997) Paracrine stimulation of interstitial collagenase (MMP-1) in the human endometrium by interleukin 1alpha and its dual block by ovarian steroids. Proc Natl Acad Sci USA 94:10341–10345CrossRefPubMedGoogle Scholar
  27. Sobin LH, Wittekind CH (eds) (2002) TNM classification of malignant tumors, 6th edn. Wiley-Liss, New York, pp 65–68Google Scholar
  28. Stelzner S, Emmrich P (1997) The mixed type in Lauren’s classification of gastric carcinoma. Histologic description and biologic behavior. Gen Diagn Pathol143:39–48Google Scholar
  29. Templeton NS, Brown PD, Levy AT, Margulies IM, Liotta LA, Stetler-Stevenson WG (1990) Cloning and characterization of human tumor cell interstitial collagenase. Cancer Res 50:5431–5437PubMedGoogle Scholar
  30. Tomimatsu S, Ichikura T, Mochizuki H (2001) Significant correlation between expression of interleukin-1alpha and liver metastasis in gastric carcinoma. Cancer 91:1272–1276CrossRefPubMedGoogle Scholar
  31. Wyatt CA, Coon CI, Gibson JJ, Brinckerhoff CE (2002) Potential for the 2G single nucleotide polymorphism in the promoter of matrix metalloproteinase to enhance gene expression in normal stromal cells. Cancer Res 62:7200–7202PubMedGoogle Scholar
  32. Ye S, Dhillon S, Turner SJ, Bateman AC, Theaker JM, Pickering RM, Day I, Howell WM (2001) Invasiveness of cutaneous malignant melanoma is influenced by matrix metalloproteinase 1 gene polymorphism. Cancer Res 61:1296–1298PubMedGoogle Scholar
  33. Yokozaki H (2000) Molecular characteristics of eight gastric cancer cell lines established in Japan. Pathol Int 50:767–777CrossRefPubMedGoogle Scholar
  34. Zhu Y, Spitz MR, Lei L, Mills GB, Wu X (2001) A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter enhances lung cancer susceptibility. Cancer Res 61:7825–7829PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Shunji Matsumura
    • 1
  • Naohide Oue
    • 1
  • Yasuhiko Kitadai
    • 2
  • Kazuaki Chayama
    • 2
  • Kazuhiro Yoshida
    • 3
  • Yoshiyuki Yamaguchi
    • 3
  • Tetsuya Toge
    • 3
  • Kazue Imai
    • 4
  • Kei Nakachi
    • 4
  • Wataru Yasui
    • 1
  1. 1.Department of Molecular PathologyHiroshima University Graduate School of Biomedical SciencesHiroshimaJapan
  2. 2.Department of Medicine and Molecular ScienceHiroshima University Graduate School of Biomedical SciencesHiroshimaJapan
  3. 3.Department of Surgical OncologyResearch Institute for Radiation Biology and Medicine, Hiroshima UniversityHiroshimaJapan
  4. 4.Department of Radiobiology/Molecular EpidemiologyRadiation Effects Research FoundationHiroshimaJapan

Personalised recommendations