Clinicopathological significance of MMP-2 and TIMP-2 genotypes in gastric cancer.
OBJECTIVE
Single nucleotide polymorphisms in matrix metalloproteinase-2 (MMP-2) -1306 C/T and tissue inhibitor of metalloproteinase-2 (TIMP-2) -418 G/C abolish the Sp-1 binding site and down-regulate expression of these genes. We aim to elucidate the role of MMP-2 and TIMP-2 in clinicopathological manifestations of gastric cancer.


METHODS
We enrolled 240 gastric cancer patients and 283 controls. DNA was extracted from peripheral blood leucocytes. MMP-2 and TIMP-2 genotypes were analysed by PCR-direct sequencing and PCR-RFLP method, respectively.


RESULTS
MMP-2 and TIMP-2 genotypes were not associated with gastric cancer development. However, patients with MMP-2 -1306 C/C genotype showed higher risk of lymphatic invasion (odds ratio (OR)=2.77, p=0.01) and venous invasion (OR=2.93, p=0.012). TIMP-2 G/G genotype was associated with serosal invasion (OR=1.89, p=0.009), lymph node metastasis (OR=2.19, p=0.021), lymphatic invasion (OR=2.87, p=0.016) and venous invasion (OR=2.65, p=0.033).


CONCLUSIONS
Our results suggest MMP-2 and TIMP-2 genotypes play a crucial role in gastric cancer invasion, but not with development of gastric cancer.
Wu
Chun-Ying
CY
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Wu
Ming-Shiang
MS
Chen
Yi-Ju
YJ
Chen
Chien-Jen
CJ
Chen
Hsiao-Ping
HP
Shun
Chia-Tung
CT
Chen
Gran-Hum
GH
Huang
Shih-Pei
SP
Lin
Jaw-Town
JT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D018365:Neoplasm, Residual / Q000235:genetics / Q000401:mortality / Q000473:pathology; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
D009363:Neoplasm Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2