Association Between the ACE (I/D) Gene Polymorphism and Hepatocellular Carcinoma Risk in Egyptian HCV Patients

Abstract

Background: Hepatocellular carcinoma is one of the most fatal malignancies worldwide and is related to many risk factors. Chronic HCV is associated with a 20–30-fold increased risk for HCC. Angiotensin-converting enzyme (ACE) is overexpressed in many cancers and plays a major role in angiogenesis and carcinogenesis. Aim: We aimed to elucidate the effect of the ACE I/D gene polymorphism in patients with HCV-related liver cirrhosis and HCC, and its relationship to clinical parameters. Patients and Methods: The study included 180 participants, cirrhotic (n=60), HCC (n=60) and control healthy subjects (n=60). Liver and renal function tests, alpha-fetoprotein, HCV antibodies and triphasic CT were assessed. ACE Gene polymorphism was assessed by Nested PCR. Results: We observed higher frequencies of DD (36.7%) and DI (51.7%) genotypes, along with the D allele (62.5%), in HCC patients compared to those of cirrhotic cases (10%, 40% and 30%, respectively) and control subjects (6.7%, 38.3%, and 25.8%, respectively). DD and DI genotypes increased the risk and predicted the occurrence of HCC by OR 25.932 and OR 6.354, respectively. The D allele conveys significant risk for HCC compared to control and cirrhotic groups with OR 4.785 and OR 3.889, respectively. Both DD genotype and D allele are significantly correlated with larger tumor size and metastasis. Conclusion: The ACE I/D polymorphism (DD genotype and D allele) is significantly associated with HCC risk in HCV patients and is correlated with increased tumor growth and advanced stage.