TY - JOUR AB - 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 m1 (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 m1 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/m1, 1.04 for m1/m1 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 m1 allele of CYP1A1 [wt/m1: odds ratio (OR)=5.68, P=0.0080; m1/m1: 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/m1/GSTM1null: OR=19.14, P=0.0030; m1/m1/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. AD - Center of Pharmacological and Toxicological Research (IFT), Molecular and Clinical Pharmacology Program, Biomedical Sciences Institute, Faculty of Medicine, University of Chile, P.O. Box 70111, Santiago 7, Chile null AU - Cordero,Karina AU - Espinoza,Iris AU - Caceres,Dante AU - Roco,Angela AU - Miranda,Carla AU - Squicciarini,Valentina AU - Santander,Paula AU - Lee,Kuen AU - Saavedra,Iván AU - Quiñones,Luis DA - 2010/05/01 DO - 10.3892/ol_00000097 EP - 553 IS - 3 JO - Oncol Lett PY - 2010 SN - 1792-1074 1792-1082 SP - 549 ST - Oral cancer susceptibility associated with the CYP1A1 and GSTM1 genotypes in Chilean individuals T2 - Oncology Letters TI - Oral cancer susceptibility associated with the CYP1A1 and GSTM1 genotypes in Chilean individuals UR - https://doi.org/10.3892/ol_00000097 VL - 1 ER -