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Distinct genotype-dependent differences in transcriptome responses in humans exposed to environmental carcinogens
Almudena Espín-Pérez, Theo M C M de Kok, Danyel G J Jennen
1Department of Public Health, Ghent University, 9000 Ghent, Belgium.
Carcinogenesis
|August 3, 2015
Summary
Genetic variability influences how environmental carcinogens affect gene expression and cancer risk. Males show a stronger response, and individuals with more risk alleles may face higher risks from combined exposures.
Area of Science:
- Environmental Health
- Genetics
- Molecular Biology
Background:
- Individual cancer risk assessment benefits from considering genetic variability alongside environmental carcinogen exposure.
- Understanding gene expression changes related to carcinogen exposure is key to identifying susceptible individuals.
Purpose of the Study:
- To investigate the impact of genetic polymorphisms on the relationship between environmental carcinogen exposure and gene expression.
- To identify exposure-dependent coregulated genes and pathways involved in carcinogenesis.
Main Methods:
- Mixed-effects models analyzed gene expression data from 134 subjects against multiple carcinogen exposures, 28 polymorphisms, and other factors.
- Biological interpretation of outcomes was performed using ConsensusPathDB, focusing on cancer-related pathways.
- Combined exposure to cadmium, lead, PCBs, DDE, HCB, and 1-OH-pyrene was evaluated.
Main Results:
- Both sexes showed deregulated generic and carcinogenesis-related pathways, with males exhibiting a stronger transcriptome response.
- Key genes linked to cancer development, including NOTCH1 and ITGB3, were identified.
- Individuals with higher numbers of risk alleles demonstrated increased responsiveness in cancer-related gene expression to combined carcinogen exposure.
Conclusions:
- Genetic polymorphisms significantly modulate the transcriptome response to combined environmental carcinogen exposure.
- Specific genes like NOTCH1 and ITGB3 are implicated in individual cancer risk due to environmental factors.
- This highlights the importance of integrating genetic susceptibility into environmental health risk assessments for personalized cancer prevention.
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