الفهرس 
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Abstract
Hepatocellular carcinoma (HCC) is a type of cancer that affects the liver. Rarely is it found early. 85–90% of all liver cancers that start in the liver are caused by HCC. It is the fifth most common type of cancer in the world and the second leading cause of cancer deaths. Cirrhosis of the liver, chronic infection with the hepatitis B virus (HBV), hepatitis C virus (HCV), double or triple chronic infection with HBV, HCV, and hepatitis delta virus (HDV), long-term heavy alcohol use, obesity, smoking, and type II diabetes are the main risk factors for HCC. In addition to the known patient-specific risk factors for HCC in CHB listed above, single-nucleotide polymorphisms also put people at risk (SNPs). A number of SNPs have been linked to HCC. , and profiles of how they are expressed have been made. Cytokines have been looked at as possible biomarkers that could be used to predict the different stages of HCC and learn more about how it happens. When risk factors for HCC are present, the initial inflammatory response in the liver does not go away. As a result, the imbalanced expression of cytokines encourages a chronic healing response. By encouraging hepatocytes to divide and grow back, which can cause mutations and set the stage for HCC to form., this reaction may contribute to the development of fibrosis, cirrhosis, and eventually HCC. Because cytokines are present at all phases of HCC growth, analysing them could provide useful information for HCC identification and management. The capacity to identify cytokines in serum and/or plasma could be employed as biomarkers to improve early HCC detection rates and disease outcome, as well as as prognostic indicators in response to therapy.
Polymorphisms in cytokine-coding genes can affect the production and function of these proteins, as well as disease susceptibility and progression. The IL-33/St2 pathway, TNF-, and IL-10 are among the most interesting.
The main aim of this study was to find the association between certain polymorphisms in the following cytokines with the risk of HCC; -IL33/ST2 pathway, IL10 and TNF alpha. This case control study was conducted on 100 cases and 100 controls. Cases were recruited from the Minia university Hospital and El Raey El Saleh hospital in the period between December 2018 and May 2021. Blood samples were obtained from all individuals after giving informed consent and after obtaining an approval from the Research Ethical Committee of faculty of Medicine, Minia University, Minia, Egypt.
The main findings of the study revealed that:
Regarding IL33\ST2 polymorphisms; rs7025417 and rs3821204 respectively, observed genotype frequencies of the 2 SNPs (C and T allels) were significantly associated with increased HCC risk for IL33 rs7025417 only (p value =0.002 and 0.93 for rs7025417 and rs3821204, respectively). In multivariate logistic regression, The IL33rs7025417 CT and TT genotypes were both linked to a higher risk of HCC (odds ratio =0.03 and 0.01 respectively). Compared to the combined genotypes of rs7025417TT-rs3821204GG (OR=1.86, 95 percent CI, 1.19–2.90, P=0.006), the combined genotypes of rs7025417TT-rs3821204CG/CC were linked to a significantly higher risk of HCC. (OR=1.86, 95 percent CI, 1.19–2.90, P=0.006).
For IL10 polymorphisms rs1800896 and rs1800871, genotype frequencies of the 2 SNPs (G\A and C\T for rs1800896 and rs1800871 respectively) showed significant association with increased HCC risk for IL10rs1800871 only (p value = 0.001 for and 0.336 for rs1800871 and rs1800896, respectively). CC genotype in rs1800871 was significantly associated with HCC risk (odds ratio=0.04). The AA genotype in IL 10 rs1800896 was more frequent in HCC cases than in control but the difference was statistically not significant.
For TNF-alpha polymorphism at -308 (rs1800629), there was significant difference and association between this SNP (G\A allels) and increasing risk of HCC. The observed GG, GA and AA genotype distribution was 55%, 27% and 19% in cases and 22%, 26% and 51% in controls respectively with p value of 0.0001. By multivariate logistic regression GG genotype was associated with increased HCC risk and AA genotype was associated with decreased HCC risk with OR=0.0001 for both.
Regarding allel frequency distribution, no significant association was found with HCC except in TNF-alpha rs1800629 which show significant increase in G allel in cases than in control (P=0.0001).
Serum level of IL 33 and IL 10 were measured using ELISA and the results were calculated by five parameter curve. Both IL levels show significant association with risk of HCC, P value was 0.049 and 0.001 for IL 10 and 33 respectively.
Based on our findings we recommend for further studies on larger sample size and larger geographic scale for more validation and further researches of the mechanism of these polymorphisms in the development and progression of HCC, which will aid in the development of better preventative and treatment options.