Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Genetic polymorphisms in tumour suppressor genes and genes encoding xenobiotic metabolising enzymes alter the activity of their corresponding enzymes and are important individual susceptibility factors for NSCLC. Because of the lack of information in literature, the aim of our study was to investigate the role of the tumour suppressor gene TP53 (Arg72Pro) and the xenobiotic metabolising CYP2E1*5B gene polymorphisms on the risk of NSCLC development. The study population consisted of 172 patients and 172 controls (156 men and 16 women in each group). Genetic polymorphisms were determined with real-time polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). Multivariate analysis showed a significant association with NSCLC for the combination between the TP53 codon72 Arg/Pro and the Pro/Pro genotypes (OR 2.21, 95 % CI 1.39-3.51; p=0.001). We also analysed whether combinations of these gene variants with GSTM1, GSTT1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) gene polymorphisms were associated with the NSCLC risk. A significant increase in the risk was observed for the following combinations: TP53 codon72 variant with GSTM1 null (OR 2.22, 95 % CI 1.23-4.04; p=0.009), GSTT1 null (OR 2.98, 95 % CI 1.49-5.94; p=0.002), and GSTP1 (Ala114Val) variant genotypes (OR 3.38, p=0.002). Further studies with larger samples are needed to verify these findings. KEY WORDS: carcinogen metabolism; CYP2E1; genetic polymorphism; GST; NSCLCLung cancer is the most common cancer type in the world, which affects men in particular. It is also the leading cause of death among cancers (1). Histologically, about 80 % of lung cancers are non-small cell lung carcinomas (NSCLC). The inbuilt phase I and II biotransformation enzyme systems inactivate environmental carcinogens, especially those present in tobacco smoke, depending on the regulating polymorphisms. Epidemiological studies show that genetic differences and interactions among genetic variants might modify lung cancer susceptibility (2, 3). Therefore, it is important to identify individual genetic and acquired factors that modify lung cancer risk in order to develop preventive strategies based on this information. This is particularly true for identifying polymorphisms of tumour suppressor genes and xenobiotic metabolising enzyme genes. The TP53 tumour suppressor gene is an essential regulator of the cell-cycle arrest, DNA repair, and apoptosis (4). An important single nucleotide polymorphism detected in TP53 is Arg72Pro. This allele has been shown to decrease the activity of the corresponding protein, which is crucial for the apoptotic function of TP53 (5, 6). Recent studies have reported the association between this polymorphism and lung cancer (7-11).CYP2E1 is an important phase I biotransformation enzyme that transforms N-nitrosamines, vinyl chloride, and benzene in tobacco smoke into mutagenic and carcinogenic metabolites (12). In NSCLC patients it has been fou...

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