Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome

Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To dat...

Full description

Saved in:
Bibliographic Details
Published in:Journal of exposure science & environmental epidemiology 2015-05, Vol.25 (3), p.256-263
Main Authors: Tanase, Anna-Maria, Marchio, Agnès, Dumitrascu, Traian, Dima, Simona, Herlea, Vlad, Oprisan, Gabriela, Dejean, Anne, Popescu, Irinel, Pineau, Pascal
Format: Article
Language:English
Subjects:
631/208/737
692/699/67/1504/1610
692/699/67/2324
704/172
Adult
Aflatoxin B1
Aflatoxins
Aged
Analysis
Biochemistry, Molecular Biology
Biomarkers, Tumor - genetics
Cancer
Carcinoma, Hepatocellular - chemically induced
Carcinoma, Hepatocellular - genetics
Chemical mutagenesis
Deoxyribonucleic acid
DNA
DNA, Mitochondrial - drug effects
Environmental aspects
Environmental Exposure - adverse effects
Environmental factors
Environmental Pollutants - toxicity
Epidemiology
Female
Gene expression
Gene mutations
Genes
Genetic aspects
Genetic Markers
Genomic analysis
Genomics
Hepatitis
Hepatocellular carcinoma
Hepatoma
Human health and pathology
Humans
Hépatology and Gastroenterology
Life Sciences
Liver cancer
Liver Neoplasms - chemically induced
Liver Neoplasms - genetics
Male
Medicine
Medicine & Public Health
Middle Aged
Mitochondria
Mortality
Mutation
NRF2 protein
Oncology, Experimental
original-article
Oxidative stress
Oxidative Stress - drug effects
Oxidative Stress - genetics
p53 Protein
Point Mutation - drug effects
Pollutants
Prospective Studies
Risk analysis
Risk Factors
Romania
Tumors
Western Europe
β-Catenin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To date, HCC from this country has not been subject to molecular characterization. We analyzed a series of 48 consecutive HCC cases. Point mutations were searched in 9 nuclear genes and the mitochondrial D-loop. Oxidative stress response was monitored through measurement of gene expression ( NRF2 , KEAP1 , SRXN1 , and CES1 ) by qRT-PCR. An atypical mutation spectrum was observed, as more than 40% of DNA changes were oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected primarily genes encoding for β -catenin and NRF2 ( P
ISSN:1559-0631
1559-064X
DOI:10.1038/jes.2014.16