Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden

No hay miniatura disponible
Marchio, Agnès
Cerapio, Juan Pablo
Ruiz, Eloy
Cano, Luis
Casavilca, Sandro
Terris, Benoît
Deharo, Eric
Dejean, Anne
Bertani, Stéphane
Pineau, Pascal
Título de la revista
Revista ISSN
Título del volumen
Nature Publishing Group
Proyectos de investigación
Unidades organizativas
Número de la revista
In Peru, hepatocellular carcinoma (HCC) arises in young non-cirrhotic patients. Hepatitis B virus (HBV) is suspected to be the prominent etiological agent. We thus performed a comprehensive molecular study of HBV infection in 65 Peruvian HCC patients. Only 51% were considered as persistently infected at the onset. HBV DNA was found by PCR in the tumor and/or matched non-tumor liver tissues in more than 80% of cases (n = 53/65). HBV DNA was significantly more abundant in livers of younger patients than in those of the older ones. We consistently observed low viral DNA burden (0.1–6.5 copies for 100 cells), with viral genomes in younger patients displaying higher proportion of mutations at di-pyrimidines (TpT and CpC, P = 0.006). A drastic activation of multiple DNA repair pathways in tumors of younger patients was observed. Our observations clearly challenge the current vision that associates high HBV DNA load with earlier tumor development. We concluded that in Peru, and maybe in other populations with Americas’ indigenous ancestry, HBV-associated liver tumorigenesis might differ significantly from that generally observed in the rest of the world. Procedures used to screen for HCC development in subjects at risk should be adapted to the local situation. © 2018, The Author(s).
This study was funded by the French National League against Cancer (team label LNCC) and Odyssey-RE; E.D., S.B., and P.P. were supported by the Third Cancer Plan, ITMO Cancer of the French National Alliance for Life Sciences and Health (ENV201408); J.P.C. was a recipient of a doctoral fellowship from the Peruvian National Council for Science and Technology (212-2015-FONDECYT); L.C. was a recipient of a doctoral fellowship from French National Research Institute for Sustainable Development (IRD) (EMHE-ARTS-2016-878573B); and L.C., E.R., and S.C. were supported by the Young Research Teams Associated with IRD Program (INCAncer). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors wish to acknowledge all patients whose participation was essential to the achievement of this study. The authors are grateful to Karina Cancino, Dany Cordova, Franco Doimi, Macarena Farías, and Maricarmen Valera from the Cancer Research Biobank of the Department of Pathology of INEN for their leadership in aggregating the medical records and collecting the biomedical specimens. We thank Damien Mornico for his considerable help in viral sequence submissions and Lucas Robinson for his valuable editorial assistance.
Palabras clave
Hepatitis B virus, chronic hepatitis B, DNA repair, female, genetics