A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer.
OBJECTIVE
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.
Matsumura
Shunji
S
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan.
Oue
Naohide
N
Nakayama
Hirofumi
H
Kitadai
Yasuhiko
Y
Yoshida
Kazuhiro
K
Yamaguchi
Yoshiyuki
Y
Imai
Kazue
K
Nakachi
Kei
K
Matsusaki
Keisuke
K
Chayama
Kazuaki
K
Yasui
Wataru
W
D000368:Aged; D016022:Case-Control Studies; D003596:Cytosine; D005260:Female; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*; D013941:Thymine
D003596:Cytosine; D020780:Matrix Metalloproteinase 9; D013941:Thymine