RECK gene polymorphisms in hepatitis B-related hepatocellular carcinoma: A case-control study

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the fourth most common cancer in Egypt where chronic hepatitis C is the most common underlying etiology. Worldwide, HCC is the fourth most common cause of cancer-related mortality. In Egypt, it is the most common cause of cancer-related morbidity and mortality [1]. Hepatic carcinogenesis is a complex process with multiple underlying factors and pathways. Both personal genetic and environmental factors influence the evolution of HCC. Thus, the occurrence of HCC varies across patients [2]. Understanding these biological factors may help identify patients who are most likely to benefit from particular preventative strategies or screening policies. Numerous genetic analyzes have highlighted the association between single nucleotide polymorphisms (SNPs) as an underlying factor of HCC [[2], [3], [4], [5], [6]].

Chronic hepatitis B virus (HBV) infection is responsible for over 50 % of HCC cases around the world [7]. In Egypt, the incidence of chronic HBV infection decreased significantly in the general population following the introduction of universal HBV vaccination for infants in 1992 [8]. The rates of HBV surface antigen and HBV core total antibody positivity among those aged 15–59 years in Egypt are 1.5 % and 15.7 %, respectively [9]. HBV genotype D is the most common genotype among Egyptians; however, genotype E caused a breakthrough infection after the national HBV vaccination campaign in Egypt [10].

The development of HCC in patients with chronic HBV infection is related to differences in the HBV genotype, genetic variations, tumor-specific somatic mutations, and environmental factors. The identification of viral and host variations can improve the rate of early diagnosis and prognosis whereas the identification of somatic mutations promoting hepato-carcinogenesis can guide precision therapy for patients with HCC. Ten genotypes of HBV (A to J) were identified, with genotype D being associated with a higher risk of HCC. The risk of HCC is similar in genotypes A and D [11].

HBV infection causes HCC when the viral proteins disturb the hepatocyte signaling pathways and, thus, affect gene expression and function, or when HBV DNA integrates the host genome to induce chromosomal instability and chronic inflammation that alters specific signaling pathways [11]. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) is a cell membrane-anchored type of glycoprotein that may act as a metastasis suppressor against activated Ras oncogenes [12]. It is widely expressed in normal tissues [13]. In animal models, RECK expression inhibits tumor invasion, metastasis, and angiogenesis. High RECK expression in tumor tissues also is associated with better survival [14]. Thus, the upregulation of RECK may be a promising approach for treating malignant tumors [15]. This study aimed to identify possible associations between the RECK gene polymorphism rs10814325 and the risk of developing HCC among Egyptian patients with chronic HBV.

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