Back to Search
Start Over
Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome.
- Source :
-
Journal of exposure science & environmental epidemiology [J Expo Sci Environ Epidemiol] 2015 May; Vol. 25 (3), pp. 256-63. Date of Electronic Publication: 2014 Apr 16. - Publication Year :
- 2015
-
Abstract
- 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<0.0001). Besides, tumors from patients born in Greater Bucharest carried TP53 mutations more frequently than others (45 vs 10%, P=0.02). Finally, a R249S mutation of TP53, well-known hallmark of aflatoxin B1 exposure, was found. Our findings indicate, therefore, that distinct mutagenic processes affect Romanian patients with HCC. Further analyses are now warranted in order to identify causal lifestyle or environmental factors.
- Subjects :
- Adult
Aged
Carcinoma, Hepatocellular chemically induced
DNA, Mitochondrial drug effects
Female
Genetic Markers
Humans
Liver Neoplasms chemically induced
Male
Middle Aged
Oxidative Stress drug effects
Oxidative Stress genetics
Prospective Studies
Risk Factors
Romania
Biomarkers, Tumor genetics
Carcinoma, Hepatocellular genetics
Environmental Exposure adverse effects
Environmental Pollutants toxicity
Liver Neoplasms genetics
Point Mutation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1559-064X
- Volume :
- 25
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of exposure science & environmental epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 24736102
- Full Text :
- https://doi.org/10.1038/jes.2014.16