The genotypes of IL-1 beta and MMP-3 are associated with the prognosis of HCV-related hepatocellular carcinoma.
OBJECTIVE
Cytokines and matrix metalloproteinases (MMPs) are involved in tumor growth, invasion, and remote metastasis in various cancers. Recently, functional gene polymorphisms in these cytokines and MMPs have been found, and some reports have revealed an association between these polymorphisms and the prognosis of various cancers. In this study, we examined the relationship between the gene polymorphisms of interleukin 1 beta (IL-1b), IL-1 receptor antagonist (IL-1 RN), transforming growth factor beta 1 (TGF-b1), MMP-1, MMP-3, and MMP-9 and the prognosis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).


METHODS
We enrolled 92 HCV-related HCC patients in the study, and gene polymorphisms of IL-1b -31 C/T, IL-1 RN variable number of tandem repeats (VNTR), TGF-b1 +869 C/T, MMP-1 -1,607 1G/2G, MMP-3 -1,171 5A/6A, and MMP-9 -1,562 C/T were analyzed.


RESULTS
In HCC clinical features, TGF-b1 C carriers and MMP-3 5A carriers had significantly larger HCC diameters than TGF-b1 T and MMP-3 6A homozygotes. In HCC prognosis, IL-1b T homozygotes and MMP-3 5A carriers had a significantly poorer prognosis than IL-1b C carriers and MMP-3 6A homozygotes. Those with a combination of IL-1b T homozygosity and MMP-3 5A had synergistically poorer HCC prognosis.


CONCLUSIONS
The IL-1b -31 T allele and MMP-3 5A allele are cooperative risk factors for poor prognosis in HCC patients, suggesting that these gene polymorphisms might be potential markers for predicting the prognosis of HCC patients.
Okamoto
Kinya
K
The Second Department of Internal Medicine, Tottori University School of Medicine, Yonago. okamotka@grape.med.tottori-u.ac.jp
Ishida
Chihiro
C
Ikebuchi
Yuichiro
Y
Mandai
Mari
M
Mimura
Kenichi
K
Murawaki
Yoshikazu
Y
Yuasa
Isao
I
D000368:Aged; D000483:Alleles; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000150:complications; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors
D017931:DNA Primers; D004273:DNA, Neoplasm; D053583:Interleukin-1beta; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3