Genetics modulate hepatocellular cancer in alcoholic cirrhosis

Polymorphisms in antioxidant enzymes modulate hepatic iron accumulation and hepatocellular carcinoma development in alcoholic patients with cirrhosis, finds the latest issue of Cancer Research.

Manganese superoxide dismutase converts the superoxide anion into H₂O₂.

Unless this is detoxified by glutathione peroxidase-1, it can increase hepatic iron and react with iron to form genotoxic compounds.

Dr Angela Sutton and colleagues assessed the role of Ala/Val- manganese superoxide dismutase and Pro/Leu- glutathione peroxidase 1 polymorphisms in hepatic iron accumulation.

The researchers also evaluated the role of these genotypes in hepatocellular carcinoma development in patients with alcoholic cirrhosis.

The 2 Val-manganese superoxide dismutase alleles indicate slow H₂O₂ production.

Stainable iron is a risk factor for hepatocellular carcinoma

Cancer Research

The 2 Pro-glutathione peroxidase-1 alleles presumably indicate quick H₂O₂ detoxification.

Genotypes were determined in 162 alcoholic patients with cirrhosis but without hepatocellular carcinoma initially.

The patients were prospectively followed up for hepatocellular carcinoma development.

The research team found that patients with 2 Val-manganese superoxide dismutase alleles, and 2 Pro-glutathione peroxidase-1 alleles had a lower risk of hepatocellular carcinoma than other patients.

Indeed, hepatocellular carcinoma did not occur in subjects with this "2 Val-manganese superoxide dismutase/2 Pro-glutathione peroxidase-1" genotype.

It occurred in 16% of "2Val-manganese superoxide dismutase/1 or 2 Leu-glutathione peroxidase-1," and 27% of "1 or 2 Ala-manganese superoxide dismutase /2 Pro-glutathione peroxidase-1 patients,"

Hepatocellular carcinoma occurred in 32% of "1 or 2 Ala-manganese superoxide dismutase/1 or 2 Leu-glutathione peroxidase-1" patients.

The percentage of patients with stainable hepatic iron increased progressively with these genotypic associations, at 22%, 28%, 50%, and 53%, respectively.

The team observed that stainable iron was a risk factor for hepatocellular carcinoma.

Dr Sutton's team concluded, “Polymorphisms in antioxidant enzymes modulate hepatic iron accumulation and hepatocellular carcinoma development in French alcoholic patients with cirrhosis.”