J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, and C. Mathers, Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012, International Journal of Cancer, vol.13, issue.5, 2014.
DOI : 10.1002/ijc.29210

J. Yang and L. Roberts, Hepatocellular carcinoma: a global view, Nature Reviews Gastroenterology & Hepatology, vol.150, issue.8, pp.448-458, 2010.
DOI : 10.1038/nrgastro.2010.100

K. Mcglynn and W. London, Epidemiology and natural history of hepatocellular carcinoma, Best Practice & Research Clinical Gastroenterology, vol.19, issue.1, pp.3-23, 2005.
DOI : 10.1016/j.bpg.2004.10.004

P. Goss, B. Lee, T. Badonivac-crnjevic, K. Strasser-weippl, and Y. Chavarri-guerra, Planning cancer control in Latin America and the Caribbean, The Lancet Oncology, vol.14, issue.5, pp.391-436, 2013.
DOI : 10.1016/S1470-2045(13)70048-2

E. Ruiz, J. Sanchez, J. Celis, E. Payet, and F. Berrospi, Short and long-term results of liver resection for hepatocellular carcinoma in Peru: a Peruvian single center experience on 232 cases, Rev Gastoenterol Peru, vol.27, pp.223-237, 2007.

S. Bertani, P. Pineau, S. Loli, J. Moura, and M. Zimic, An Atypical Age-Specific Pattern of Hepatocellular Carcinoma in Peru: A Threat for Andean Populations, PLoS ONE, vol.37, issue.6, p.67756, 2013.
DOI : 10.1371/journal.pone.0067756.t001
URL : https://hal.archives-ouvertes.fr/hal-01356600

A. Bleyer, R. Barr, B. Hayes-lattin, D. Thomas, and C. Ellis, The distinctive biology of cancer in adolescents and young adults, Nature Reviews Cancer, vol.106, issue.4, pp.288-298, 2008.
DOI : 10.1038/nrc2349

P. Pineau, . Marchio, C. Battiston, E. Cordina, and A. Russo, Chromosome instability in human hepatocellular carcinoma depends on p53 status and aflatoxin exposure, Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol.653, issue.1-2, pp.6-13, 2008.
DOI : 10.1016/j.mrgentox.2008.01.012

J. Vandesompele, D. Preter, K. Pattyn, F. Poppe, B. et al., Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes, Genome Biol, vol.3, p.34, 2002.

A. Teschendorff, A. Naderi, N. Barbosa-morais, and C. Caldas, PACK: Profile Analysis using Clustering and Kurtosis to find molecular classifiers in cancer, Bioinformatics, vol.22, issue.18, pp.2269-2275, 2006.
DOI : 10.1093/bioinformatics/btl174

J. Wang, S. Wen, W. Symmans, L. Pusztai, and K. Coombes, The bimodality index: a criterion for discovering and ranking bimodal signatures from cancer gene expression profiling data, Cancer Inform, vol.7, pp.199-216, 2009.

J. Kenney and E. Keeping, Mathematics of statistics: Part 1, 1962.

C. Cabezas, Viral hepatitis B: epidemiology and bases for its control, Rev Peru Med Exp Salud Publica, vol.24, pp.378-397, 2007.

C. Vogel, P. Anthony, N. Mody, and L. Barker, HEPATITIS-ASSOCIATED ANTIGEN IN UGANDAN PATIENTS WITH HEPATOCELLULAR CARCINOMA, The Lancet, vol.296, issue.7674, pp.621-624, 1970.
DOI : 10.1016/S0140-6736(70)91396-6

G. Macnab, J. Urbanowicz, E. Geddes, and M. Kew, Hepatitis-B surface antigen and antibody in Bantu patients with primary hepatocellular cancer, British Journal of Cancer, vol.33, issue.5, pp.544-548, 1976.
DOI : 10.1038/bjc.1976.86

A. Sjä-lander, R. Birgander, A. Kivela, and G. Beckman, p53 Polymorphisms and Haplotypes in Different Ethnic Groups, Human Heredity, vol.45, issue.3, pp.144-149, 1995.
DOI : 10.1159/000154275

A. Tanase, A. Marchio, T. Dumitrascu, S. Dima, and V. Herlea, Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome, Journal of Exposure Science and Environmental Epidemiology, vol.7, issue.3, 2014.
DOI : 10.1093/ije/dyr236

Y. Tsang, M. Deavers, C. Sun, S. Kwan, and E. Kuo, ) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma, The Journal of Pathology, vol.23, issue.4, pp.449-456, 2013.
DOI : 10.1002/path.4252

C. Guichard, G. Amaddeo, S. Imbeaud, Y. Ladeiro, and L. Pelletier, Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma, Nature Genetics, vol.44, issue.6, pp.694-698, 2012.
DOI : 10.1006/meth.2001.1262
URL : https://hal.archives-ouvertes.fr/inserm-00719917

G. Bond, W. Hu, E. Bond, H. Robins, and S. Lutzker, A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans, Cell, vol.119, issue.5, pp.591-602, 2004.
DOI : 10.1016/j.cell.2004.11.022

S. Wilkening, J. Bermejo, and K. Hemminki, MDM2 SNP309 and cancer risk: a combined analysis, Carcinogenesis, vol.28, issue.11, pp.2262-2267, 2007.
DOI : 10.1093/carcin/bgm191

J. Sandoval, D. Lacerda, M. Jota, A. Salazar-granara, and P. Vieira, The Genetic History of Indigenous Populations of the Peruvian and Bolivian Altiplano: The Legacy of the Uros, PLoS ONE, vol.145, issue.10, p.73006, 2013.
DOI : 10.1371/journal.pone.0073006.s010

W. Hong and K. Guan, The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway, Seminars in Cell & Developmental Biology, vol.23, issue.7, pp.785-793, 2012.
DOI : 10.1016/j.semcdb.2012.05.004

D. Tschaharganeh, X. Chen, P. Latzko, M. Malz, and M. Gaida, Yes-Associated Protein Up-regulates Jagged-1 and Activates the NOTCH Pathway in Human Hepatocellular Carcinoma, Gastroenterology, vol.144, issue.7, pp.1530-1542, 2013.
DOI : 10.1053/j.gastro.2013.02.009

M. Kew, Alpha-fetoprotein in primary liver cancer and other diseases., Gut, vol.15, issue.10, pp.814-821, 1974.
DOI : 10.1136/gut.15.10.814

B. Spear, Alpha-fetoprotein gene regulation: lessons from transgenic mice, Seminars in Cancer Biology, vol.9, issue.2, pp.109-116, 1999.
DOI : 10.1006/scbi.1998.0087

H. El-serag, Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma, Gastroenterology, vol.142, issue.6, pp.1264-1273, 2012.
DOI : 10.1053/j.gastro.2011.12.061

S. Thorgeirsson and J. Grisham, Molecular pathogenesis of human hepatocellular carcinoma, Nature Genetics, vol.31, issue.4, pp.339-346, 2002.
DOI : 10.1038/ng0802-339

E. Fassio, S. Díaz, C. Santa, M. Reig, M. Artola et al., Etiology of hepatocellular carcinoma in Latin America: a prospective, multicenter, international study, Ann Hepatol, vol.9, pp.63-69, 2010.

S. Indacochea, R. Bueno, D. La-fuente, J. Ferrufino, and J. , [Liver cancer in hyperendemic area of B and delta hepatitis: report of 19 cases, Rev Gastroenterol Peru, vol.17, pp.56-59, 1997.

E. Ruiz, M. Almonte, R. Pizarro, J. Celis, and J. Montalbelti, [Hepatitis B and C virus infection as risk factors for hepatocarcinoma in Peru: case and control study, Rev Gastroenterol Peru, vol.18, pp.199-212, 1998.

S. Van-rensburg, P. Cook-mozaffari, D. Van-schalkwyk, J. Van-der-watt, and T. Vincent, Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei, British Journal of Cancer, vol.51, issue.5, pp.713-726, 1985.
DOI : 10.1038/bjc.1985.107

K. Szymañ-ska, J. Chen, Y. Cui, Y. Gong, and P. Turner, TP53 R249S mutations, exposure to aflatoxin, and occurrence of hepatocellular carcinoma in a cohort of chronic hepatitis B virus carries from Qidong, China, Cancer Epidemiol Biomarkers Prev, vol.18, pp.638-643, 2009.

S. Smalley, C. Moertel, J. Hilton, L. Weiland, and H. Weiand, Hepatoma in the noncirrhotic liver, Cancer, vol.27, issue.7, pp.1414-1424, 1988.
DOI : 10.1002/1097-0142(19881001)62:7<1414::AID-CNCR2820620729>3.0.CO;2-7

F. Trevisani, M. Frigerio, V. Santi, A. Grignaschi, and M. Bernardi, Hepatocellular carcinoma in non-cirrhotic liver: A reappraisal, Digestive and Liver Disease, vol.42, issue.5, pp.341-347, 2010.
DOI : 10.1016/j.dld.2009.09.002

H. Huang, H. Fujii, A. Sankila, B. Mahler-araujo, and M. Matsuda, ??-Catenin Mutations Are Frequent in Human Hepatocellular Carcinomas Associated with Hepatitis C Virus Infection, The American Journal of Pathology, vol.155, issue.6, pp.1795-1801, 1999.
DOI : 10.1016/S0002-9440(10)65496-X

H. Hsu, Y. Jeng, T. Mao, J. Chu, and P. Lai, ??-Catenin Mutations Are Associated with a Subset of Low-Stage Hepatocellular Carcinoma Negative for Hepatitis B Virus and with Favorable Prognosis, The American Journal of Pathology, vol.157, issue.3, pp.763-770, 2000.
DOI : 10.1016/S0002-9440(10)64590-7

P. Laurent-puig, P. Legoix, O. Bluteau, J. Belghiti, and D. Franco, Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis, Gastroenterology, vol.120, issue.7, pp.1763-1773, 2001.
DOI : 10.1053/gast.2001.24798

S. Boyault, D. Rickman, A. De-reyniè-s, C. Baladaud, and S. Rebouissou, Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets, Hepatology, vol.12, issue.1, pp.42-52, 2007.
DOI : 10.1002/hep.21467
URL : https://hal.archives-ouvertes.fr/inserm-00130313

C. Caldas, S. Hahn, L. Da-costa, M. Redston, and M. Schutte, Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma, Nature Genetics, vol.7, issue.1, pp.27-32, 1994.
DOI : 10.1016/0002-9610(91)90371-J

T. Shuin, K. Kondo, S. Torigoe, T. Kishida, and Y. Kubota, Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas, Cancer Res, vol.54, pp.2852-2855, 1994.

M. Greenblatt, A. Grollman, and C. Harris, Deletions and insertions in the p53 tumor supressor gene in human cancers: confirmation of the DNA polymerase slippage/misalignment model, Cancer Res, vol.56, pp.2130-2136, 1996.

D. Solt, E. Cayama, H. Tsuda, K. Enomoto, and G. Lee, Promotion of liver cancer development by brief exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or carbon tetrachloride, Cancer Res, vol.43, pp.188-191, 1983.

M. Garcia-diaz and T. Kunkel, Mechanism of a genetic glissando*: structural biology of indel mutations, Trends in Biochemical Sciences, vol.31, issue.4, pp.206-213, 2006.
DOI : 10.1016/j.tibs.2006.02.004

D. Bisceglie and A. , Issues in screening and surveillance for hepatocellular carcinoma, Gastroenterology, vol.127, issue.5, pp.104-107, 2004.
DOI : 10.1053/j.gastro.2004.09.022

J. Gillespie and V. Uversky, Structure and function of ??-fetoprotein: a biophysical overview, Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, vol.1480, issue.1-2, pp.41-56, 2000.
DOI : 10.1016/S0167-4838(00)00104-7

R. Bei and G. Mizejewski, Alpha Fetoprotein is More than a Hepatocellular Cancer Biomarker: From Spontaneous Immune Response in Cancer Patients to the Development of an AFP-Based Cancer Vaccine, Current Molecular Medicine, vol.11, issue.7, pp.564-581, 2011.
DOI : 10.2174/156652411800615162

G. Tsoulfas, A. Mekras, P. Agorastou, and D. Kiskinis, Surgical treatment for large hepatocellular carcinoma: does size matter?, ANZ Journal of Surgery, vol.6, issue.7-8, pp.510-517, 2012.
DOI : 10.1111/j.1445-2197.2012.06079.x

J. O9brien, E. Dvorin, A. Drugan, M. Johnson, and Y. Yaron, Race-Ethnicity-Specific Variation in Multiple-Marker Biochemical Screening, Obstetrical & Gynecological Survey, vol.89, issue.3, pp.355-358, 1997.
DOI : 10.1097/00006250-199703000-00007

P. Bryant-greenwood, J. O9brien, X. Huang, Y. Yaron, and M. Ayoub, Maternal Weight Differences Do Not Explain Ethnic Differences in Biochemical Screening, Fetal Diagnosis and Therapy, vol.13, issue.1, pp.46-48, 1998.
DOI : 10.1159/000020801

F. Becker, A. Horland, A. Shurgin, and S. Sell, A study of alpha1-fetoprotein levels during exposure to 39-methyl-4-dimethylaminoazobenzene and its analogs, Cancer Res, vol.35, pp.1510-1513, 1975.

P. Sizaret, A. Tuyns, N. Martel, A. Jouvenceaux, and A. Levin, ?-FETOPROTEIN LEVELS IN NORMAL MALES FROM SEVEN ETHNIC GROUPS WITH DIFFERENT HEPATOCELLULAR CARCINOMA RISKS, Annals of the New York Academy of Sciences, vol.31, issue.1 Carcinofetal, pp.136-155, 1975.
DOI : 10.1002/1097-0142(197006)25:6<1261::AID-CNCR2820250603>3.0.CO;2-J

S. Sell, K. Xu, W. Huff, L. Kabena, and R. Harvey, Aflatoxin exposure produces serum alphafetoprotein elevations and marked oval cell proliferation in young male Pekin ducklings, Pathology, vol.30, issue.1, pp.34-39, 1998.
DOI : 10.1080/00313029800169645

J. Koropatnick and M. Cherian, Exposure to different forms of cadmium in mice: Differences in metallothionein and alphafetoprotein mRNA induction in liver and kidney, Journal of Biochemical Toxicology, vol.699, issue.3, pp.159-172, 1988.
DOI : 10.1002/jbt.2570030304

R. Scott, S. Chakraborty, S. Sell, J. Hunt, and H. Dunsford, Change in the ploidy state of rat liver cells during chemical hepatocarcinogenesis and its relationship to the increased expression of alphafetoprotein, Cancer Res, vol.49, pp.6085-6090, 1989.

M. Kew, L. Van-staden, and A. Bellingan, Serum, alpha-fetoprotein concentrations in urban and rural Southern African blacks with hepatocellular carcinoma, Trop Gastroenterol, vol.16, pp.11-15, 1995.

K. Nuttall, R. Lenke, and E. Ashwood, Maternal serum??-fetoprotein and altitude, Medical Hypotheses, vol.54, issue.3, pp.498-500, 2000.
DOI : 10.1054/mehy.1999.0884

B. Bois-joyeux, M. Denissenko, H. Thomassin, S. Guesdon, and R. Ikonomova, The c-jun proto-oncogene down-regulates the rat alpha-fetoprotein promoter in HepG2 hepatoma cells without binding to DNA, J Biol Chem, vol.270, pp.10204-10211, 1995.

T. Magee, Y. Cai, M. El-houseini, J. Locker, and Y. Wan, Retinoic Acid Mediates Down-regulation of the ??-Fetoprotein Gene through Decreased Expression of Hepatocyte Nuclear Factors, Journal of Biological Chemistry, vol.273, issue.45, pp.30024-30032, 1998.
DOI : 10.1074/jbc.273.45.30024

M. Peterson, C. Ma, and B. Spear, Zhx2 and Zbtb20: Novel regulators of postnatal alpha-fetoprotein repression and their potential role in gene reactivation during liver cancer, Seminars in Cancer Biology, vol.21, issue.1, pp.21-27, 2011.
DOI : 10.1016/j.semcancer.2011.01.001

S. Bertani, S. Sauer, E. Bolotin, and F. Sauer, RETRACTED: The Noncoding RNA Mistral Activates Hoxa6 and Hoxa7 Expression and Stem Cell Differentiation by Recruiting MLL1 to Chromatin, Molecular Cell, vol.43, issue.6, pp.1040-1046, 2011.
DOI : 10.1016/j.molcel.2011.08.019

A. Villasante, D. Piazolla, H. Li, G. Gomez-lopez, and M. Djalabo, expression by Ezh2 in pluripotent stem cells, Cell Cycle, vol.10, issue.9, pp.1488-1498, 2011.
DOI : 10.4161/cc.10.9.15658

C. Sun, L. Sun, K. Jiang, D. Gao, and X. Kang, NANOG promotes liver cancer cell invasion by inducing epithelial???mesenchymal transition through NODAL/SMAD3 signaling pathway, The International Journal of Biochemistry & Cell Biology, vol.45, issue.6, pp.1099-1108, 2013.
DOI : 10.1016/j.biocel.2013.02.017

E. Kohler, E. Colleen, I. Chatterjee, A. Malik, and K. Wary, NANOG induction of fetal liver kinase-1 (FLK1) transcription regulates endothelial cell proliferation and angiogenesis, Blood, vol.117, issue.5, pp.1761-1769, 2011.
DOI : 10.1182/blood-2010-07-295261

M. Wang, S. Chiou, and C. Wu, Targeting cancer stem cells: emerging role of Nanog transcription factor, Onco Targets Ther, vol.6, pp.1207-1220, 2013.

T. Yamashita and X. Wang, Cancer stem cells in the development of liver cancer, Journal of Clinical Investigation, vol.123, issue.5, pp.1911-1918, 2013.
DOI : 10.1172/JCI66024

M. O9connor, D. Xiang, S. Shigdar, J. Macdonald, and Y. Li, Cancer stem cells: A contentious hypothesis now moving forward, Cancer Letters, vol.344, issue.2, pp.180-187, 2014.
DOI : 10.1016/j.canlet.2013.11.012

A. Logrieco, A. Moretti, C. Altomare, A. Bottalico, and E. Torres, Occurrence and toxicity ofFusarium subglutinans from Peruvian maize, Mycopathologia, vol.96, issue.3, pp.185-190, 1993.
DOI : 10.1007/BF01103480

L. Marcos, A. Bussalleu, A. Terashima, and J. Espinoza, Detection of antibodies against Fasciola hepatica in cirrhotic patients from Peru, Journal of Helminthology, vol.81, issue.01, pp.23-26, 2009.
DOI : 10.1016/0166-6851(83)90047-6

C. Yacoub, A. Pé-rez-foguet, and N. Miralles, Trace Metal Content of Sediments Close to Mine Sites in the Andean Region, The Scientific World Journal, vol.51, issue.3, p.732519, 2012.
DOI : 10.1016/j.clay.2010.10.029