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Abstract Hepatocellular carcinoma (HCC) is one of the most common types of cancer in the world, accounting for 85–90 % of the total primary liver cancer burden worldwide. It is also the third most frequent cause of cancer-related mortality. In Egypt, HCC is the second and sixth most common malignancy in men and women; respectively. The rising incidence of HCC may be due to high prevalence of HCV and its complications. HCV infection causes inflammation of the liver and a variable grade of damage to the organ that over decades can lead to cirrhosis. Previous reports identified two specific genetic factors to HCVrelated HCC, the Dishevelled, Egl-10 and Pleckstrin Domain-Containing 5 (DEPDC5) locus and the MHC class I polypeptide-related sequence A (MICA) locus in Japanese patients. DEPDC5 gene is located on the long arm of chromosome 22, 22q12.3 and it encodes a cytoplasmic protein which has been lately shown to have an important function in focal epilepsy, a neurological disorder. DEPDC5 protein has been established to block the effect of mammalian target of rapamycin (mTOR), a multi-functional protein participated in many cellular process including inflammation, growth of the cell and tumor formation including hepatocarcinogenesis. MICA is localized on chromosome 6p21. MICA is a membrane protein that is up-regulated in various cancer cells and also stimulated in response to various cellular stresses such as infection, hypoxia, and heat shock. It is an essential part of the innate immune response, where MICA can be linked to the natural killer group 2 member D receptor and then activate NK cells and CD8+ cells. The catechol-O-methyltransferase (COMT) gene is localized on chromosome 22q11.2. It is a vital enzyme participated in the inactivation of endogenous catecholamine and catechol estrogens. Catechol estrogens have the capability to destroy DNA and carcinogenetic agents. So, the damage, the loss of or changes in COMT is hypothetically contributed to genomic instability and tumor formation. The aim of the current study was to investigate the association of the DEPDC5 (rs1012068), MICA (rs2596542) and COMT (rs4680) with HCC risk related HCV cases in Egypt. One hundred HCC cases were recruited from National Cancer Institute, Cairo University and one hundred healthy controls were recruited from National Liver Institute, Manoufia University. Ten ml of blood was withdrawn from all cases and controls under a complete aseptic condition in two vacutainer tubes containing EDTA. One tube of each sample was centrifuged at 2000 rpm for 10 min, plasma and buffy coat were separated, aliquoted and stored at −80°C. Plasma samples were used for the determination of HCV Ab, HBsAg, and AFP. AST, ALT, TBIL, ALB. Also, plasma was used to perform in-house RT HCV PCR for the detection of HCV. Buffy coat was used for detection of polymorphism of DEPDC5, MICA and COMT genes by real time PCR technique, the other whole blood tube was used for determination of HB and platelets. No significant variation was found between the two studied groups in age and gender (P = 0.365 and 0.626 respectively), this is due to selection criteria. In addition, HCV infection (100%) is detected in HCC group. The laboratory parameters such as AFP, liver enzymes (ALT, AST), TBIL, ALB, HB and platelet count were detected in the two studied group. The levels of AFP, AST, ALT and TBIL were significantly increased in HCC group compared to the controls. On the other hand, the platelet count and HB concentration were significantly decreased. Out of the three gene polymorphisms analyzed, the DEPDC5 and MICA variants were significantly related with the development of HCC (P < 0.0001) among HCV-infected patients, while COMT is not associated with HCC risk (P = 0.607). Only the DEPDC5 variants showed a high (P < 0.0001) significant difference in patients with cirrhosis. No significant percentage was demonstrated on the levels of the three gene polymorphisms in gender and age except the COMT was observed in aged patients (P = 0.018). Moreover, Studying DEPDC5, MICA and COMT variants with some biochemical and hematological parameters showed no significant association between the SNPs and some of the studied parameters as AFP, ALT, AST, TBIL, ALB, HB and platelets, but only the DEPDC5 variants were significantly correlated with low platelets count (P < 0.045). In conclusion, the current findings suggested that the genetic polymorphisms in DEPDC5 (rs1012068) and MICA (rs2596542), but not COMT (rs4680) are significantly associated with HCC development in Egyptian patients with HCV infection. |