الفهرس 
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Abstract
Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer in the world (Donato et al., 2006). Hepatocarcinogenesis is a multistep process with a multifactorial etiology. Chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), and cirrhosis of any etiology are the major risk factors for HCC (Kremsdorf et al., 2006). Overall, 75% to 80% of HCC cases are attributable to persistent viral infections with either HBV (50–55%) or HCV (25–30%) (Suruki et al., 2006).
Cytokines, as the products of host response to inflammation, play an important role in the defense against viral infections. However, in HCV infection they may play a prominent role in liver damage (Koziel, 1999). Interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α) are key cytokines in the inflammatory response (Dinarello, 1996). Interleukin 1 beta (IL-1β) is one of the potent pro-inflammatory cytokines and has a wide array of biological functions, including cell survival and proliferation (Roshak et al., 1996). Some single nucleotide polymorphisms (SNPs) have been reported in IL-1β, from which cytosine (C)/ thymidine (T) base transitions at –31 bp from the transcriptional start site. It has been shown that the –31T allele enhances IL-1β transcriptional activity (El-Omar et al., 2000) and a number of studies reported that –511C/–31T is a risk haplotype for the development of cancer (Chang et al., 2005). Another cytokine that has an important influence on IL-1β levels is the IL-1 receptor antagonist (IL-1RN); the gene encoding this cytokine; IL-1RN, is also known to be polymorphic (Santtila et al., 1998). This work aimed to investigate the relationship between the gene polymorphisms of interleukin-1 beta (IL-1β), IL-1 receptor antagonist (IL-1RN) and tumor necrosis factor alpha (TNF-α) and the development HCV-related HCC.
The study included 170 subjects; 100 patients attending outpatient clinic of internal medicine department in Mansoura University Hospital diagnosed as HCV (50 patients with HCC and 50 patients without HCC) and 70 healthy individuals with no liver affection (mean age/years ± SD; 55.24±5.72). The patients were subjected to full history taking and thorough physical examination.General physical examination included examination of metabolic, endocrine, cardiovascular, respiratory, gastro-intestinal and neurological systems to exclude presence of abnormalities.
Three ml venous blood samples were taken from each patient and control and collected on tubes containing EDTA and stored at –20°C for DNA extraction , then gene polymorphisms of IL-1β –31 C/T, IL-1β –511 C/T, IL-1RN variable number of tandem repeats (VNTR), and TNF-α –308 G/A were investigated by PCR based assay.
PCR determination of genotypes frequencies of IL-1β –31, IL-1β –511, IL-1RN VNTR and TNF-α –308 shown that there were significant increase in the frequency of IL-1β –31TT, IL-1RNA2A2 and TNF-α –308AA genotypes in HCC group when compared to control. In addition, there was significant increase in IL-1RN A2A2 genotype frequency in HCV patients without HCC when compared to control group (<0.05). However, no significant difference in IL-1β–511 genotype frequencies between different groups.
Analysis of allele frequencies of IL-1β –31, IL-1β –511, IL-1RN VNTR and TNF-α –308 shown that there were significant increase in the frequency of IL-1β –31T, IL-1RNA2 and TNF-α –308A alleles in HCC group when compared to control (All p < 0.05, OR (95% CI) = 2(1.2-3.5), 4.3(2.4-7.8) and 2.3(1.7-6.4), respectively. In addition, there was significant increase in IL-1RNA2 allele frequency in HCV patients without HCC when compared to control group (< 0.001, OR (95% CI) =3.8(2.1-6.9). However, no significant difference in IL-1β –511 allele frequencies between different groups.
Conclusion and recommendations: IL-1, IL-1RN VNTR, and TNF-α genes polymorphisms could be risk factors for the development of HCC in patients with chronic HCV in Egyptian population , and to confirm this results, large number of cases and other risk factors should be studied in the future.