Genetic polymorphism of CYP1A1, GSTM1 and GSTT1 genes in Indian oral cancer

Oral cancer ranks first among all cancers in males and is the third most co mmon among females in India. Tobacco-derived carcinogens are involved in th e development of oral cancer. Environment-gene interaction in oral carcinog enesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study looked at the significance of gen etic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in patients with oral c ancer. The study included 98 oral cancer patients and 60 age and sex matche d healthy controls. Genotypes of CYP1A1, GSTM1 and GSTT1 were determined by PCR-RFLP. GSTM1 null deletion was observed in 49% of oral cancer cases and 33% of control subjects. For GSTT1, 18% of carcinomas and 8% of controls h ad the null genotype. In the case of CYP1A1 m2 allele, 51% of oral cancers and 17% of normal controls, respectively, had one or both alleles with the isoleucine --> valine substitution. Digestion of the PCR products with enzy me Nco1 revealed polymorphism for CYP1A1 m2 with bands at 263 bp. There was no association between genotypes with tumor size, stage, grade, and age. S ince null genotype individuals may possibly be poor detoxifiers with reduce d ability to neutralise the reactive carcinogenic intermediates, they may b e a high risk category. The frequency distribution of CYP1A1 m2 (Ile/val) g enotypes among oral cancer patients was significantly different that from n ormal controls. The risk of CYP1A1 can be supported by the functional diffe rence between presence of valine and isoleucine; valine type has higher cat alytic and mutagenic activity towards benzo[a] pyrene than the isoleucine t ype, In conclusion, our results suggest that polymorphism in CYP1A1 m2 gene and/or GSTM1 and GSTT1 null genotype may confer an increased risk for oral cancer. (C) 2001 Elsevier Science Ltd. All rights reserved.