Molecular epidemiologic study on lung cancer susceptibility

Cytochrome P4501A1(CYP1A1)and glutathione S-transferases(GSTs)are considered to be responsible for the activation or inactivation of benzo(A)pyrene(BP)and other polycyclic aromatic hydrocarbons in cigarette smoke to carcinogens。We investigated polymorphisms of CYP1A1(Msp I and Ile-Val)and GSTs(M1 And T1)in 189lung cancer patients。We also measured phenotypic activity of CYP1A1(aryl hydrocarbon hydroxylase，AHH)in peripheral mitogen-treated lymphocytes.No relationship was observed between age-，cigarette dose-and season of the year-adjusted AHH activity and histologic type of tumor or TNM stage。Adjusted AHH inducibility of genotype C(geometric mean and 95%confidence interval(CI)；17.8and114.0-22.7)in Msp I polymorphism was significantly higher than those of the other two genotypes(P&lt；0.0001)，while no significant difference was observed between genotypes A(5.0 and 6.0)and B(5.5 and 4.7-6.4)。On the other hand，non-induced AHH activity of genotype Val/Val(0.141and0.105-0.190pmol/min/10 I D 16 I D 1 cells)in isoleucinevaline(Ile-Val)polymorphism was significantly higher than those of genotypes Ile/Ile(0.035 and 0.030-0.41 pmol/min/10 I D 16 D 1 cells)and Ile/Val(0.034 and 0.027-0.43 pmol/min/10 I D 16 D 1 cells)。Irrespective of histologic type，TNM stage，CYP1A1 genotype or GSTM1 genotype，aromatic-DNA adduct levels were not distinguishable.Variant genotype at the Msp I site associated with high AHH inducibility，while variant genotype in Ile-Val polymorphism was significantly related to increased the level of CYP1A1 alytic activity.This association among lung cancer patients was more exaggerated than healthy controls reported previously.

Cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs) are considered to be responsible for the activation or inactivation of benzo(a)pyrene (BP) and other polycyclic aromatic hydrocarbons in cigarette smoke to carcinogens. We investigated polymorphisms of CYP1A1 (Msp I and Ile-Val) and GSTs (M1 and T1) in 189 lung cancer patients. We also measured phenotypic activity of CYP1A1(aryl hydrocarbon hydroxylase, AHH) in peripheral mitogen-treated lymphocytes.No relationship was observed between age-, cigarette dose- and season of the year-adjusted AHH activity and histologic type of tumor or TNM stage. Adjusted AHH inducibility of genotype C (geometric mean and 95% confidence interval (CI) ; 17.8 and 114.0-22.7) in Msp I polymorphism was significantly higher than those of the other two genotypes (P<0.0001), while no significant difference was observed between genotypes A (5.0 and 6.0) and B (5.5 and 4.7-6.4). On the other hand, non-induced AHH activity of genotype Val/Val (0.141 and 0.105-0.190pmol/min/10ィイD16ィエD1 cells) in isoleucinevaline (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.035 and 0.030-0.41 pmol/min/10ィイD16ィエD1 cells) and Ile/Val (0.034 and 0.027-0.43 pmol/min/10ィイD16ィエD1 cells) (P<0.0001). Irrespective of histologic type, TNM stage, CYP1A1 genotype or GSTM1 genotype, aromatic-DNA adduct levels were not distinguishable.Variant genotype at the Msp I site associated with high AHH inducibility, while variant genotype in Ile-Val polymorphism was significantly related to increased the level of CYP1A1 catalytic activity. This association among lung cancer patients was more exaggerated than healthy controls reported previously.