GSTM1 and NAT2 polymorphisms in operable and non-operable lung cancer patients

We have genotyped 657 Norwegian men, including 282 lung cancer patients (14 7 non-operable and 135 operable) and 375 healthy referents (210 smokers and 165 nonsmokers), to study the possibility that glutathione S-transferase M 1 (GSTM1)-null and/or N-acetyl transferase 2 (NAT2)-slow genotypes confer s usceptibility towards lung cancer in smokers. Compared with smoking referen ts, there was a significant over-representation of the GSTM1-null genotype among patients with squamous cell carcinoma (SQ) [odds ratio (OR) = 1.7, 95 % confidence interval (95%CI) = 1.1-2.7], and the NAT2-slow genotype among patients with large cell carcinoma or mixed histological diagnosis (LM) (OR = 2.5, 95%CI = 1.0-6.1). In contrast to operable patients, non-operable pa tients showed a clear over-representation of slow genotypes if they were yo unger (less than or equal to 63 years; versus older: OR = 3.9, 95%CI = 1.7- 8.8) or younger light smokers [less than or equal to 30 pack-years (PY); ve rsus heavy smokers: OR = 5.7, 95%CI = 1.4-23.3]. Among younger light smoker s, the slow genotype appeared to be associated with an increased risk of de veloping nonoperable tumours only (OR = 6.3, 95%CI = 1.9-20.4), especially other types of tumours than SQ (OR = 10.8, 95%CI = 1.4-83.9). The null geno type (OR = 3.9, 95%CI 1.1-13.5) and the null/slow combination (OR = 4.5, 95 %CI = 1.5-13.8) seemed to increase the risk for nonoperable SQ only. These results are supported by logistic regressions of patients allowing interact ions between tumour type (or treatment) and PY (or age), and indicate that the GSTM1-null genotype could be an important susceptibility factor for SQ while the NAT2-slow genotype may have an impact on other types of lung canc er. Individuals with the GSTM1-null and/or NAT2-slow genotypes may constitu te susceptible groups with increased risk to contract non-operable lung can cer at younger age and lower smoking dose.