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Association between CYP2E1 polymorphisms and risk of differentiated thyroid carcinoma
Lucia Pellé1, Monica Cipollini1, Roman Tremmel2,3
1Department of Biology, University of Pisa, via Derna 1, 56126, Pisa, Italy.
Archives of Toxicology
|January 20, 2016
Summary
Genetic variations in the cytochrome P450 2E1 (CYP2E1) enzyme may influence differentiated thyroid carcinoma (DTC) risk. Specific CYP2E1 genotypes are linked to altered acrylamide (AA) metabolism and DTC susceptibility.
Area of Science:
- Genetics
- Environmental Health
- Endocrinology
Background:
- Differentiated thyroid carcinoma (DTC) arises from complex genetic and environmental interactions.
- Dietary acrylamide (AA), a food processing byproduct, is a potential environmental factor for DTC.
- Cytochrome P450 2E1 (CYP2E1) metabolizes AA to glycidamide (GA), and its polymorphisms may affect DTC risk.
Purpose of the Study:
- To investigate the association between CYP2E1 genetic variations and the risk of developing DTC.
- To explore the functional impact of identified CYP2E1 genotypes on enzyme activity and expression.
Main Methods:
- Case-control studies (discovery and replication) analyzed four haplotype tagging SNPs (ht-SNPs) in the CYP2E1 locus.
- Genotyping for rs2480258 and association analysis with DTC risk were performed.
- CYP2E1 mRNA, protein expression, and enzymatic activity were measured in human liver samples.
Main Results:
- A significant association was found between rs2480258 and DTC risk, with specific genotypes showing increased odds ratios.
- The minor allele of rs2480258 was linked to lower CYP2E1 mRNA and protein levels.
- Reduced CYP2E1 enzymatic activity was observed in individuals with the minor allele.
Conclusions:
- Inter-individual differences in CYP2E1 activity, influenced by genetic polymorphisms, may modulate DTC risk.
- This suggests that exposure to xenobiotics like acrylamide could play a role in DTC development.
- CYP2E1 genotype may serve as a biomarker for assessing susceptibility to environmentally induced thyroid cancer.
Keywords:
Case–control association studyCytochrome P450 2E1Differentiated thyroid carcinomaGenetic susceptibilityPolymorphismsMore Related Videos
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