A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer

  • Shunji Matsumura
  • Naohide Oue
  • Hirofumi Nakayama
  • Yasuhiko Kitadai
  • Kazuhiro Yoshida
  • Yoshiyuki Yamaguchi
  • Kazue Imai
  • Kei Nakachi
  • Keisuke Matsusaki
  • Kazuaki Chayama
  • Wataru Yasui
Original Paper

Abstract

Purpose

Matrix metalloproteinase-9 (MMP-9, gelatinase B) plays a key role in cancer invasion and metastasis by degradating the extracellular matrix (ECM) and basement membrane barriers. A cytosine (C)-thymidine (T) single nucleotide polymorphism (SNP) at position –1562 in the MMP-9 promoter is reported to affect expression of this gene. The purpose of this study was to investigate the relation between the –1562 C/T polymorphism and the development and progression of gastric cancer.

Methods

The study population included 177 gastric cancer patients and 224 healthy control subjects. The SNP in the MMP-9 promoter was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Genotype frequencies were compared between patients and controls, and the association of genotypes with clinicopathological features was studied.

Results

Genotype frequencies in gastric cancer patients were similar to those in control subjects (P = 0.223). However, significant association was found between degree of tumor invasion, clinical stage, and lymphatic invasion and the MMP-9 polymorphism in gastric cancer patients (P<0.05, for each).

Conclusions

Our results indicate that the T allele in the MMP-9 promoter is associated with the invasive phenotype of gastric cancer.

Keywords

MMP-9 SNP Gastric cancer Depth of tumor invasion Lymphatic invasion 

Abbreviations

MMP-9

Matrix metalloproteinase-9

SNP

Single nucleotide polymorphism

C

Cytosine

T

Thymidine

RFLP

Restriction fragment length polymorphism

ECM

Extracellular matrix

PCR

Polymerase chain reaction

OR

Odds ratio

CI

Confidence interval

Notes

Acknowledgements

We thank Masayoshi Takatani and Mutsumi Ueda, Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, for their excellent technical assistance and advice

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Shunji Matsumura
    • 1
  • Naohide Oue
    • 1
  • Hirofumi Nakayama
    • 1
  • Yasuhiko Kitadai
    • 2
  • Kazuhiro Yoshida
    • 3
  • Yoshiyuki Yamaguchi
    • 3
  • Kazue Imai
    • 4
  • Kei Nakachi
    • 4
  • Keisuke Matsusaki
    • 5
  • Kazuaki Chayama
    • 2
  • 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 Oncology, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan
  4. 4.Department of Radiobiology/Molecular EpidemiologyRadiation Effects Research FoundationHiroshimaJapan
  5. 5.Department of SurgeryHofu Institute of GastroenterologyYamaguchiJapan

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