Cytochrome P450 2E1 and head and neck cancer: Interaction with genetic and environmental risk factors

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.

DNA Repair Gene XRCC1 Polymorphisms and Head and Neck Cancer Risk: An Updated Meta-Analysis Including 16344 Subjects

“…Of these, two papers were excluded due to the fact that they did not evaluate the association between HNC risk and XRCC1 polymorphisms [23,24]. Subsequently, five studies were excluded because of the lack of useful genotype data [25–29]. In the remaining 31 studies, two papers were excluded because of overlapping data [30,31].…”

The PstI/RsaI and DraI polymorphisms of CYP2E1and head and neck cancer risk: a meta-analysis based on 21 case-control studies

“…One study [18] was discarded for insufficient data (although we tried to contact the authors to query the data), two [19,20] were discarded as being studies on leukoplakia. As shown in table 1, 21 case-control studies finally met our criteria for inclusion [2,3,7,21-38]. 21 studies were identified for the CYP2E1 -PstI/RsaI polymorphism, including a total of 4951 cases and 5995 controls, and for the DraI polymorphism 9 studies were identified covering a total of 2510 cases and 2162 controls.…”

“…It is hypothesized that part of the susceptibility to head and neck cancer may be determined by the inter-individual differences in the bioactivation of procarcinogens and detoxification of carcinogens. CYP2E1 , which is a major component of the microsomal system involved in the metabolism of ethanol and acetone among phase I enzymes, has been widely studied as a cause of susceptibility to head and neck cancer [2,3]. …”

Clinical features and prognostic factors in patients with head and neck cancer: Results from a multicentric study

“…Polymorphisms in genes encoding for metabolism of alcohol to acetaldehyde [alcohol dehydrogenase gene family (ADH)] and from acetaldehyde to acetate [aldehyde dehydrogenase 2 (ALDH2)], and CYP2E1 polymorphisms, are suspect in HNC and other alcohol-related cancer aetiology [10][11][12][13][14][15][16][17][18][19]. In particular, a significant protective effect of two single nucleotide polymorphisms (SNPs) towards upper aero-digestive tract cancer (UADT) was reported for two alcohol dehydrogenase genes: ADH1B (rs1229984) and ADH7 (rs1573496) [20].…”