A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer |
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Authors: | Shunji Matsumura Naohide Oue Hirofumi Nakayama Yasuhiko Kitadai Kazuhiro Yoshida Yoshiyuki Yamaguchi Kazue Imai Kei Nakachi Keisuke Matsusaki Kazuaki Chayama Wataru Yasui |
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Institution: | (1) Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551 Hiroshima, Japan;(2) Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan;(3) Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan;(4) Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan;(5) Department of Surgery, Hofu Institute of Gastroenterology, Yamaguchi, Japan |
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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. |
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Keywords: | MMP-9 SNP Gastric cancer Depth of tumor invasion Lymphatic invasion |
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