A single nucleotide polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer.
OBJECTIVE
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.
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Shunji
S
Matsumura
Naohide
N
Oue
Yasuhiko
Y
Kitadai
Kazuaki
K
Chayama
Kazuhiro
K
Yoshida
Yoshiyuki
Y
Yamaguchi
Tetsuya
T
Toge
Kazue
K
Imai
Kei
K
Nakachi
Wataru
W
Yasui
D000368:Aged; D016022:Case-Control Studies; D002454:Cell Differentiation; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D004247:DNA; D020781:Matrix Metalloproteinase 1