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Lung cancer is a leading cause of cancer mortality worldwide with smoking and occupational exposure to carcinogenic compounds as the major risk factors. Susceptibility to lung cancer is affected by existence of polymorphic genes controlling the levels of metabolic activation and detoxification of carcinogens. We have investigated 105 single nucleotide polymorphisms (SNPs) in 31 genes from the phase I and phase II metabolism genes and antioxidant defense genes for association with the risk of non-small cell lung cancer (NSCLC) in a Norwegian population-based study. Our results indicate that several SNPs in the phase I genes,CYP1B1,CYP2D6,CYP2E1andCYP3A4, are associated with the risk of NSCLC. Moreover, significant associations with multiple SNPs in the phase II genesALDH2,COMT,EPHX1,SOD2,NAT1,NAT2,GSTM3,GSTP1,GSTT2andMPOwere also found. We prioritized our findings by use of two different recently developed Bayesian statistical tools, employing conservative prior probabilities of association. When we corrected for multiple testing using these statistical tools, three novel associations of NSCLC risk with SNPs in theCYP1B1(Arg48Gly),COMT(Val158Met) andGSTT2(Met139Ile) genes were found noteworthy. However, only four of the previously reported associations with polymorphisms in theGSTP1(Ala14Val),SOD2(Val16Ala),EPHX1(His139Arg) genes and the NAT1 fast acetylator phenotype remained significantly associated with lung cancer.

A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers