Aldehyde dehydrogenase 2 polymorphism: possibly a predisposing factor to hepatocellular carcinoma in hepatitis C cirrhotics?

ABSTRACT

Hepatocellular carcinoma [HCC] is considered as a long term multistage disease with multiple genetic alteration. Aldehyde dehydrogenase 2 [ALDH2] polymorphism may modify the risk of HCC. The aim of the present work was to evaluate the role of ALDH2 polymorphism as a predisposing factor for HCC in chronic hepatitis C virus [HCV] infected patients with cirrhosis for early detection. This study included fifty five subjects divided into three groups; twenty chronic hepatitis C patients with cirrhosis [group A], twenty chronic hepatitis C patients with cirrhosis and HCC [group B] and fifteen control subjects [group C]. The included patients were subjected to history taking, clinical examination, abdominal ultrasonography and liver biopsy [whenever possible]. All the subjects enrolled in this study were analysed for ALDH2 gene polymorphism. Genomic DNA prepared from leucocytes were used for polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] technique. In addition, mitöchondrial ALDH activity was estimated in leucocytes. Of all fifty five subjects included in this study, six were heterozygous for ALDH2 gene mutation [ALDH2*1/*2] representing 10.9%, and the others were homozygous for the normal allele [ALDH2*11*1]. Non was detected to have homozygous mutant allele. The distribution among the patients groups was the same; three patients out of twenty in each group were heterozogous for the mutant gene [15%]. All the control subjects had normal homnozygous gene [ALDH2*1/*1]. The two patients' groups showed significantly higher percent of heterozygous mutant; ALDH2*1/*2 [X[2]=11.92,P=0.0027] and lower mitochondrial ALDH activity towards acetaldehyde [F=24.32, P=0.0002] in comparison to control group. However, non significant changes in both parameters were observed between the two patients' groups [P>0.05]. ALDH2 gene mutation could not be considered as a possible predictor for HCC in non alcoholic HCV-cirrhotic patients. However, these data did not exclude completely the relation to HCV infection and/or cirrhosis. Follow-up large scale studies are needed to investigate the exact link between ALDH2 mutation and cancer