The association of MMP-1, -3 and -9 genotypes with the prognosis of HCV-related hepatocellular carcinoma patients.
OBJECTIVE
Matrix metalloproteinases (MMPs) play important roles in cancer invasion and metastasis. Recently, functional gene polymorphisms in the promoter regions of MMP-1 1G/2G, MMP-3 5A/6A and MMP-9 C/T have been found, and have been reported to be associated with the prognosis of various cancers. In this study, we examined the association of the MMP-1, -3, -9 genotypes with the prognosis of hepatocellular carcinoma (HCC).


METHODS
Ninety two patients with hepatitis C virus related HCC were enrolled in the study. Genomic DNA samples were extracted from peripheral white blood cells, and gene polymorphisms of MMP-1, MMP-3and MMP-9 were analyzed by PCR-RFLP methods.


RESULTS
There were no significant differences of the survival rate between MMP-1 1G carriers and 2G homozygotes, and between MMP-9 T carriers and C homozygotes. By contrast, HCC patients with MMP-35A allele had a significantly poorer prognosis than 6A homozygotes.


CONCLUSIONS
Unlike MMP-1 and MMP-9 genotypes, MMP-3 5A allele, with higher transcriptional activity, may be a risk factor for the poor prognosis of HCC patients.
Okamoto
Kinya
K
Second Department of Internal Medicine, Department of Legal Medicine, Tottori University School of Medicine, Yonago, 683-8504 Japan.
Mandai
Mari
M
Mimura
Kenichi
K
Murawaki
Yoshikazu
Y
Yuasa
Isao
I
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000201:enzymology / Q000235:genetics; D006526:Hepatitis C / Q000201:enzymology / Q000235:genetics / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D012367:RNA, Viral / Q000302:isolation & purification; D012307:Risk Factors; D016019:Survival Analysis
D012367:RNA, Viral; D004247:DNA; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1