RESUMEN
Lung cancer is a common cause of cancer-related death. The link between risk of lung cancer susceptibility and genetic polymorphisms in metabolic enzymes is well documented. In this study, the relationships between lung cancer susceptibility and polymorphisms in the phase I metabolic enzyme genes CYP1A1, CYP2D6, and CYP2A6 were investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 168 lung carcinoma patients from the Han ethnic group of Hunan Province in Central South China. Polymorphisms of the investigated genes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and two-step allelic-specific PCR assays. No significant differences were found between the frequencies in cases and controls for the genotypes wild-type (WW), heterozygous mutant, or homozygous mutant; for CYP1A1 or CYP2D6; or for the genotypes WW, heterozygous deletion, or null genotype for CYP2A6. The three-locus model (CYP2A6/CYP1A1/CYP2D6) had a maximum test sample accuracy that was significant (P < 0.001) with a cross-validation consistency of 10. These results indicated that the three-order interaction of CYP2A6, CYP1A1, and CYP2D6 polymorphisms might increase genetic susceptibility to lung cancer. We report the involvement of a three-order interaction between CYP1A1, CYP2A6, and CYP2D6 polymorphisms in lung cancer risk in people in Central South China, although no relationship between lung cancer risk and individual gene polymorphisms was found.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2D6/genética , Neoplasias Pulmonares/etnología , Neoplasias Pulmonares/genética , Polimorfismo Genético/genética , Adulto , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , China/etnología , Citocromo P-450 CYP2A6 , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. In this study, the relationships between genetic polymorphisms of phase I metabolic enzymes including cytochrome P450 1A1 (CYP1A1), CYP2D6 and phase II metabolic enzymes such as glutathione S-transferase M1 (GSTM1) and GSTT1 and gastric carcinoma susceptibility were investigated. Genomic DNA was isolated from the peripheral blood of 129 healthy controls and 123 gastric carcinoma patients from Han ethnic group of Hunan Province located in Central South China. The genetic polymorphisms of the above mentioned enzymes were analyzed using PCR-RFLP techniques. There was no significant difference among the frequencies of CYP1A1 and/or CYP2D6 gene's wild type, heterozygous or homozygous mutations between the gastric carcinoma group and control group. But the differences among the frequencies of GSTM1 and GSTT1 null genotype between the gastric carcinoma and control group were significant (both P < 0.05). Also there were significant differences in the frequencies of GSTM1 null in high/high-middle differentiated, middle differentiated, middle-low differentiated and low differentiated gastric tumor separately. GSTM1 null showed an increased risk in middle-low differentiated and low differentiated gastric carcinoma type, but GSTT1 null was not a risk factor for the four pathological types of gastric carcinoma mentioned above. We report here that the genotypes of CYP1A1 and CYP2D6 are not associated with gastric carcinoma risk; GSTM1 null, but not GSTT1 null inheritably increases risk of some pathological types of gastric carcinoma in Han ethnic population of Hunan Province.