Povezanost polimorfizama gena TP53 i CYP2E1*5B s nemikrocelularnim karcinomom pluća

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 metabolizing 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, 95 % CI 1.54-7.41; p=0.002). Further studies with larger samples are needed to verify these findings.Nemikrocelularni karcinom pluća (engl. non-small cell lung cancer – NSCLC) najčešći je oblik karcinoma pluća. Polimorfizimi gena za supresiju tumora i gena koji kodiraju enzime za razgradnju ksenobiotika mijenjaju aktivnost tih gena te značajno utječu na individualnu sklonost nastanku NSCLC-a. Budući da u literaturi nema dovoljno saznanja o njihovu utjecaju na nastanak bolesti, cilj je ovoga ispitivanja bio utvrditi povezanost polimorfizama tumorskoga supresorskoga gena TP53 (Arg72Pro), odnosno gena CYP2E1*5B za metabolizam ksenobiotika, s rizikom od NSCLC-a. Ispitivanje je obuhvatilo 172 bolesnika s NSCLC-om i 172 kontrolna ispitanika (po 156 muškaraca i 16 žena u svakoj skupini). Genski su polimorfizmi utvrđeni polimeraznom lančanom reakcijom u stvarnom vremenu (engl. real-time polymerase chain reaction – RT-PCR) te kombinacijom PCR-a s metodom cijepanja DNA restrikcijskim enzimima (engl. restriction fragment length polymorphism – PCR-RFLP). Multivarijantna analiza upozorava na značajnu povezanost kombinacije TP53 kodon72 Arg/Pro i Pro/Pro genotipova s NSCLC-om (OR 2,21; 95 % CI 1,39-3,51; p=0,001). Također je analizirana povezanost kombinacija ovih genskih varijanta s polimorfizmima gena glutation S-tranferaze GSTM1, GSTT1, GSTP1 ekson 5 (Ile105Val) i GSTP1 ekson 6 (Ala114Val) s rizikom od NSCLC-a te utvrđeno značajno povećanje rizika kod sljedećih kombinacija: TP53 kodon72 s GSTM1 nula (OR 2,22; 95 % CI 1,23-4,04; p=0,009), GSTT1 nula (OR 2,98; 95 % CI 1,49-5,94; p=0,002) i GSTP1 (Ala114Val) (OR 3,38; 95 % CI 1,54-7,41; p=0,002). Da bi se potvrdili ovi preliminarni rezultati, potrebna su istraživanja na većim uzorcima