Association Between Metabolic-Enzyme Gene Polymorphisms And Susceptibility Of Lung Cancer By Bioinformatic

Abstract:Lung cancer is one of the most common causes of cancer-related death. The link between lung cancer susceptibility of individuals and genetic polymorphism in metabolic enzymes is well documented, but inconsistent. In this study, the relationships between genetic polymorphisms of phase I metabolic enzymes CYP1A1, CYP2D6and CYP2A6, and lung cancer susceptibility were investigated by bioinformatic.Genomic DNA was isolated from peripheral blood of201healthy controls and168lung carcinoma patients from Han ethnic group of Hunan Province located in Central South China. Primer Premier5software was applied to design PCR primers.The genetic polymorphisms of the above mentioned were analyzed using PCR-RFLP and two-step allelic specific PCR assay. The results of the sequence were analyzed by Chromas version2.22. The difference in frequencies between lung cancer group and control group was compared by using Χ2test. The genotype-phenotype correlation was examined with additive, dominant, and recessive models with logistic regression. All above computations were calculated by using the statistical package of SPSS (SPSS Inc, Chicago, Illinois, USA) version16. The multifactor-dimensionality reduction (MDR) method was used to identify high-order gene-gene interactions. MDR software (version2.0beta) was used in MDR analysis.There was no significant difference found among the frequencies of CYP1A1gene’s wild type (WW), heterozygous mutant (WM) and homozygous mutant (MM) or CYP2D6gene’s wild type (WW), heterozygous mutant (WM) and homozygous mutant (MM) or CYP2A6gene’s wild type (WW), heterozygous deletion (WD) and deleted genotype (DD) between cases and controls. But the3locus model (CYP2A6/CYP1A1/CYP2D6) had a maximum test sample accuracy with a significant probability value (P<0.001) and cross-validation consistency of10/10, which indicate that the three-order interaction of CYP2A6, CYP1A1and CYP2D6polymorphisms may increase the genetic susceptibility to lung cancer.We report here that the involvement of three-order interaction of CYP1A1, CYP2A6, CYP2D6polymorphisms with lung cancer risk in Central South Chinese people, although no relationship between lung cancer risk and individual gene polymorphism.