Promoter polymorphisms of MMP 1 and 2 genes and risk for hepatocellular carcinoma: Case-control analysis in Turkish patients
PDF
Cite
Share
Request
Original Article
VOLUME: 26 ISSUE: 2
P: 79 - 84
March 2010

Promoter polymorphisms of MMP 1 and 2 genes and risk for hepatocellular carcinoma: Case-control analysis in Turkish patients

Turk J Surg 2010;26(2):79-84
1. Ege Üniversitesi Tıp Fakiltesi, Genel Cerrahi Anabilim Dalı, İzmir, Türkiye
2. Ege Üniversitesi Tıp Fakiltesi, Çocuk Sağlığı ve Hastalıkları Moleküler Tıp Laboratuvarı, İzmir, Türkiye
3. Kent Hastanesi, Organ Nakli Merkezi, İzmir, Türkiye
No information available.
No information available
PDF
Cite
Share
Request

Abstract

Purpose: Matrix metalloproteinases are established as strong prognostic markers for hepatocellular carcinoma which is one of the most progressive and aggressive cancer types worldwide. Hepatocellular carcinoma is very common in various populations, but the pathogenetic link between MMPs is limited so far. Due to asociation with invasion in cancer metastasis, the matrix metalloproteinases MMP-1 and MMP-2 are candidate genes for predisposition to hepatocellular carcinoma. Patients and Methods: A total of 73 patients who were diagnosed as having hepatocellular carcinoma and had undergone liver transplantation were enrolled in the study. Following DNA extraction polymerase chain reaction-restriction fragment lenght polymorphism molecular genetic analyses were performed. By case-control and genotype-phenotype correlation analysis, we investigated the risk of association of MMP-1 and MMP-2 promoter polymorphisms in 73 Turkish hepatocellular carcinoma patients compared to healthy controls. Results: Genotypic distributions of the MMP2 -735 C/T and MMP1 -1607 1G/2G polymorphisms were in Hardy-Weinberg equilibrium in patient and control groups (p>0.05). In case-control analyses, the distribution of the genotypes and allele frequencies in the cases did not differ from those in the control group (p>0.05). In genotype-phenotype correlation analysis; for MMP1 -1607 1G/2G polymorphism 2G/2G genotype was associated with portal vein invasion (p<0.02). With regard to the post-transplantation results of the present study the 4-year survival rate in the patients was 77,3% and the recurrencefree survival rate in the post-transplant phase was 96,2%. Conclusion: No significant association was determined between Turkish hepatocellular carcinoma prognosis and post-transplantation metastasis and invasion with MMP2 -735 C/T and MMP1 -1607 1G/2G polymorphisms as risk predictors.

Keywords:
Hepatocellular carcinoma, matrix metalloproteinases, MMPs, single nucleotide polymorphism

References

1
Kim S., Choi Y., Choung S., Jun J. Vascular endothelial growth factor gene +405 C/G polymorphism is associated with susceptibility to advanced stage endometriosis. Human Reproduction 2005;20: 2904-2908.
2
Filik L., Oğuz D., (Treatment of Hepatocellular Carcinoma), Güncel Gastroenteroloji 2003; 7(1): 74-79.
3
Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002; 35: 519-524.
4
Llovet JM, Bustamente J, Castells A. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for design and evaluation of therapeutic trials. Hepatology 1999; 29: 62-67.
5
Sturk C, Dumont D. In: Tannock IF, Hill RP, Bristow RG, et al, eds. Basic Science of Oncology. 4th ed. New York, NY: Mc- Graw-Hill; 2005:231-248.
6
Edmondson HA, Steiner PE. Primary carcinoma of the liver: A study of 100 cases among 48900 necropsies. Cancer 1954; 7:462-503.
7
Cole P, Morrison AS. Basic issues in population screening for cancer. J Natl Cancer Inst 1980; 64: 1263-1272.
8
Davila JA, Morgan RO, Shaib Y, Shaib Y McGlynn KA, El-Serag HB. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a populationbased study. Gastroenterology 2004; 127: 1372-1380.
9
Arii S, Yamaoka Y, Futagawa S, Inoue K Kobayashi K, Kojiro M, et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. Hepatology 2000; 32:1224-1229.
10
Bismuth H, Chiche L, Adam R, Castaing D, Diamond T, Dennison A. Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg 1993; 218: 145-151.
11
Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F., et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334:693-699.
12
Karakayali H, Sevmis S, Moray G, Yilmaz U, Ozcay F, Savas NA, Arslan G, Haberal M. Liver transplantation in patients with hepatocellular carcinoma: one center's experience. Transplant Proc 2008; 40:213- 218.
13
Kiyici M, Yilmaz M, Akyildiz M, Arikan C, Aydin U, Sigirli D, Nart D, Yilmaz F Ozacar T, Karasu Z, Kilic M. Association between hepatitis B and hepatocellular carcinoma recurrence in patients undergoing liver transplantation. Transplant Proc 2008 ;40:1511-1517.
14
Haberal M, Emiroglu R, Karakayali H Moray G, Yilmaz U, Ozçay F, Bilezikci B Arslan G. Expanded criteria for hepatocellular carcinoma and liver transplantation. Int Surg 2007;92:110-115.
15
Haberal M. Liver transplantation: experience at our center. Transplant Proc 2006; 38:2111-2116.
16
Zhai Y, Qiu W, Dong XJ, Zhang XM, Xie WM, Zhang HX, Yuan XY, Zhou GQ, He FC. Functional polymorphisms in the promoters of MMP-1, MMP-2, MMP-3 MMP-9, MMP-12 and MMP-13 are not associated with hepatocellular carcinoma risk, Gut 2007;56:445-447.
17
Okamoto K, Mandai M, Mimura K, Murawaki Y, Yuasa I, The association of MMP-1, -3 and -9 genotypes with the prognosis of HCV-related hepatocellular carcinoma patients, Res Commun Mol Pathol Pharmacol 2005;117-118:77-89.
18
Akkız H., Molecular Pathogenesis of Hepatocellular Carcinoma, Turkiye Klinikleri J Int Med Sci 2007;3.