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The study investigates the association of polymorphism in glutathione S-transferases (GSTs) with susceptibility for head and neck squamous cell carcinoma (HNSCC) and its sites as well as treatment response in cases receiving chemotherapy (CT) and combination of CT-radiotherapy (CT-RT). The case-control study included 500 male cases and an equal number of healthy male controls. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between genotypes and cancer risk. An increase in the risk for HNSCC and cancers of oral cavity, larynx or pharynx was observed in cases with null genotypes of GSTM1 or GSTT1. The interaction of alcohol or tobacco with variant genotypes of GSTM1 or GSTT1 also resulted in a significant increase in the risk for HNSCC. Further, HNSCC cases carrying the null genotypes of GSTM1 and GSTT1 or variant genotypes of GSTP1 showed a significant and superior treatment response. The present data thus provides evidence for the association of polymorphisms in GSTs with risk for HNSCC and its treatment response.

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A case control study was undertaken to investigate the association of polymorphisms in cytochrome P4501A1 (CYP1A1) with squamous cell carcinoma of head and neck (HNSCC) in North Indian population. The variant genotypes of CYP1A1*2A and CYP1A1*2C were found to be overrepresented in cases when compared to controls. The HNSCC risk also increased several folds in cases with combination of variant genotypes of CYP1A1*2A or CYP1A1*2C with null genotype of glutathione-S-transferase M1 (GSTM1), a phase II enzyme, particularly in cases who were tobacco users (smokers and tobacco chewers), demonstrating the role of gene-gene and gene-environment interactions in the development of HNSCC.

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.

The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma.

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