**11. Genetic polymorphism in CYP2E1**

CYP2E1 enzyme is an important member of the cytochrome P450 family. It is a naturally ethanol-inducible enzyme involved in alcohol metabolism. Polymorphism in *Rsa*I/*Pst*I in the promoter gene region increases transcriptional activity of the gene which may play an important role in the development of esophageal carcinoma [56].

*CYP2E1 c1/c1* genotype found at increased risk for gastric cardia cancer (GCC). Individuals with this genotype and have a history of heavy cigarette smoking were at increased risk for GCC. This suggests that the interaction of the *CYP2E1* polymorphism with smoking has a great influence on susceptibility to GCC [57]. Polymorphisms in *CYP2E1* involved in the metabolism of carcinogens tobacco and alcohol, leads to Head and Neck Squamous Cell Carcinoma (HNSCC). Haplotype analysis revealed that haplotype T-A was associated with a greater than 10-fold increase in risk for HNSCC. Use of alcohol or tobacco interact with *CYP2E1* variant genotypes or with *GSTM1* or *XRCC1 and increases the* risk of HNSCC suggest the importance of gene–gene and gene–environment interactions in the development of HNSCC [58].

There was no risk of ESCC found associated with CYP2A6, CYP2E1, GSTM1 polymorphism suggest an opposite role of GSTP1 and GSTT1 polymorphisms for ESCC [59]. Gene polymorphism in GSTM1, GSTT1, GSTP1, CYP1A1 and CYP2E1 represent risk-modifying factors for ethanol related diseases in Brazilian alcoholics and controls with similar ethnic backgrounds. Also the persons with these genotypes are genetically more prone to the development of alcoholic pancreatitis and alcoholic cirrhosis, respectively [60–63].
