Coevolution with the hepatitis B virus as a possible ontology for a peculiar form of liver cancer in Native American patients

The research program in Latin America carried out by Bertani, Casavilca and collaborators described an abnormally high incidence of hepatocellular carcinoma (HCC) in young, non-cirrhotic patients originating from the Peruvian altiplano. This early-age onset of HCC is concomitant with (a) the hyper-prevalence of a hepatitis B virus (HBV) genotype endemic to the Americas and (b) the Native American ancestry of the Peruvian HCC patients.

We hypothesized that a virus-host antagonistic coevolution between this clade of HBV and the Andean human communities could be responsible for the early-age onset of HCC. Our objectives consist in measuring the impact of HBV infection as an evolutionary force acting on the human genome by (1) genotyping the HBV associated with the early-age onset of HCC, (2) characterizing the nucleotide variations in genes under HBV selective pressure in Peruvian HCC patients, (3) specifying the genetic ancestry of these patients, and (4) modeling the adaptive dynamics of individuals with Native American ancestry at risk for HBV-mediated HCC through the genetic characterization of genes that encode virus-interacting proteins.

The originality of our research is reinforced by the comparative analysis of modern DNA with ancient DNA from pre-Columbian mummies discovered in Peru. This will allow us to measure comprehensively the evolvability of HBV and HCC patients and to establish different virus-host coevolutionary scenarios.

Main coordinators : S. Bertani, Pharmadev Toulouse & S Casavilca INEN, Lima (Perou)