NAT2 and CYP1A2 polymorphisms and lung cancer risk in relation to smoking status.

ABSTRACT

We investigated the associations between lung cancer and the gene polymorphisms of the drug metabolizing enzymes, containing cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2), glutathione S-transferase class mu (GSTM1), and N-acetyltransferase 2 (NAT2). The study involved 113 lung cancer patients and 121 non-cancer controls divided into never, light and heavy smokers according to pack-years of smoking in Japanese by using PCR-RFLP. For light smokers, the lung cancer risk of NAT2 intermediate-slow was significantly increased [the adjusted odds ratio (OR) 10.9, 95% confidence intervals (95%CI) 1.75-67.5, P-value 0.010]. Moreover, never smokers having joint genotypes of NAT2 intermediate-slow and CYP1A2*1F A/A was also associated with increased the lung cancer risk (OR 4.95, 95% CI 1.19-20.6, P-value 0.028). We suggested that light smokers with intermediate-slow NAT2 activity were at highest risk for lung cancer and the gene-gene interaction based on intermediate-slow NAT2 activity and high CYP1A2 activity would be increased a lung cancer risk among never smokers.