Cytochrome P450 2E1 and head and neck cancer: interaction with genetic and environmental risk factors
Related Experiment Video
Updated: Jun 24, 2026

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Munindra Ruwali1, Anwar Jamal Khan, Parag P Shah
1Developmental Toxicology Division, Indian Institute of Toxicology Research, CSIR, Lucknow-226 001, Uttar Pradesh, India.
Abstract:
The present case-control study investigates the association of polymorphisms in cytochrome P450 2E1 (CYP2E1), involved in the metabolism of tobacco carcinogens and alcohol, with Head and Neck Squamous Cell Carcinoma (HNSCC). In addition, the interaction of CYP2E1 (CYP2E1*5B and CYP2E1*6) with other genetic factors (null genotype of glutathione-S-Transferase M1, GSTM1, X-Ray Repair Cross Complementing Group I, XRCC1 (Arg194Trp), and environmental risk factors such as alcohol and tobacco in modifying HNSCC risk were investigated. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a total of 350 male cases of HNSCC and an equal number of healthy male controls. Statistical analysis showed a significant increase in HNSCC risk in cases with variant genotypes of CYP2E1*5B (RsaI) (O.R. 3.44; 95% C.I. 1.45-8.14) and CYP2E1*6 (DraI) (O.R. 1.76; 95% C.I. 1.28-2.41). Haplotype analysis revealed that haplotype T-A was associated with a greater than 10-fold increase in risk for HNSCC. Our data also revealed a several fold increase in HNSCC risk in cases carrying a combination of variant genotypes of CYP2E1 with the null genotype of GSTM1 or XRCC1 variant genotypes. Alcohol or tobacco use (both smoking and chewing) were also found to interact with variant genotypes of CYP2E1 in significantly enhancing HNSCC risk. This increase in risk associated with an interaction of CYP2E1 genotypes with GSTM1 or XRCC1 or with tobacco and alcohol use demonstrates the importance of gene-gene and gene-environment interactions in the development of HNSCC.
Related Concept Videos
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Cancer Prevention
Some...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
