Oral cancer susceptibility associated with the CYP1A1 and GSTM1 genotypes in Chilean individuals

Abstract

Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity following their activation by xenobiotic-metabolizing enzymes to highly reactive metabolites The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these PAHs, and GSTM1 is the main enzyme responsible for its detoxification CYP1A1 and GSTM1 polymorphisms were evaluated in 124 Chilean healthy controls and 48 oral cancer patients through PCR-based restriction fragment length polymorphism In the healthy controls, frequencies of the CYP1A1 variant alleles for ml (CYP1A1*2A) and the GSTM1null genotype were found to be 0 25 and 0 19, respectively In the oral cancer patients, these frequencies were 0 33 and 0 50, respectively Thus, the GSTM1 and ml rare alleles were significantly more frequent in the oral cancer patients compared to the controls The estimated relative risk for oral cancer associated with the single genotype CYP1A1 or GSTM1 was 2 08 for wt/ml, 1 04 for ml/ml and 4 16 for the GSTM1null genotype For smokers, the estimated relative risk (adjusted by age and gender) was higher in the individuals carrying the ml allele of CYP1A1 [wt/ml odds ratio (OR)=5 68, P=0 0080, ml/ml OR=7 77, P=0 0420] or GSTM1null genotype (OR=20 81 P<0 0001) Combined genotypes CYP1A1 and GSTM1 increased the risk significantly (wt/ml/GSTM1null OR=19 14, P=0 0030, ml/ml/GSTM1null OR=21 39, P=0 0130) Taken together, these findings suggest that Chilean individuals carrying single or combined GSTM1 and CYP1A1 polymorphisms may be more susceptible to oral cancer induced by environmental tobacco smoking