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The association of glutathione peroxidase and superoxide dismutase gene polymorphisms with urothelial bladder cancer development and progression

dc.contributor.advisorDragićević, Dejan
dc.contributor.otherMatić, Marija
dc.contributor.otherDžamić, Zoran
dc.contributor.otherPlješa-Ercegovac, Marija
dc.contributor.otherMarušić, Goran
dc.creatorNikić, Predrag
dc.date.accessioned2019-01-31T12:45:49Z
dc.date.available2019-01-31T12:45:49Z
dc.date.available2020-07-03T08:49:59Z
dc.date.issued2018-07-13
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6578
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/10714
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:19358/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=50784527
dc.description.abstractSmatra se da oksidativni stres može imati ulogu u nastanku i progresiji karcinoma. Prvi sistem odbrane od oksidativnog stresa čine antioksidantni enzimi glutation peroksidaza 1 (GPX1) i superoksid dismutaza 2 (SOD2). Kod oba antioksidantna enzima uočen je genetski polimorfizam koji rezultuje njihovom izmenjenom enzimskom aktivnosti. U ovoj studiji ispitivana je povezanost genetskih varijanti GPX1 i SOD2 sa rizikom za nastanak urotelijalnog karcinoma mokraćne bešike (UKMB), kao i moguća interakcija ovih genetskih varijanti sa poznatim faktorima rizika na rizik za nastanak UKMB. Pored toga, određivan je uticaj genetskog polimorfizma GPX1 i SOD2 na fenotipske karakteristike tumora, kao što su stadijum bolesti i histološki gradus tumora. Dodatno je procenjivana potencijalna prognostička uloga genetskih varijanti GPX1 i SOD2 u preživljavanju pacijenata sa metastatskim UKMB koji su lečeni hemioterapijom na bazi cisplatina. Materijal i Metode: U ovu prospektivnu studiju bilo je uključeno 330 pacijenata sa urotelijalnim karcinomom mokraćne bešike (prosečne starosti 65 ± 10,3 godina) i 227 zdravih osoba koje su činile kontrolnu grupu (prosečne starosti 63,4 ± 7,9 godina). Polimorfizam GPX1 (rs1050450) gena je bio određivan polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) metodom, a polimorfizam SOD2 (rs4880) gena je bio određivan metodom kvantitativnog PCR (q-PCR). U cilju ispitivanja uticaja GPX1 i SOD2 genotipova na ukupno preživljavanje, pacijenti sa metastatskim UKMB koji su primali cisplatin baziranu hemioterapiju praćeni su u periodu od dve godine. Za procenu značajnosti razlike u frekvenciji dobijenih genotipova između ispitivanih bolesnika i kontrolne grupe korišćen je χ2 test. Efekti genetskog polimorfizma GPX1 i SOD2, nezavisno ili u kombinaciji, i rizika za nastanak urotelijalnog karcinoma mokraćne bešike su procenjivani pomoću univarijantne logističke regresije. Ukupno preživljavanje pacijenata bilo je određivano Kaplan–Meier-ovom analizom preživljavanja i logrank testom za procenu prognostičkog značaja...sr
dc.description.abstractOxidative stress is thought to be involved in cancer development and progression. Glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2) play key roles in first line antioxidative defense. For both of them, genetic polymorphisms, resulting in altered enzyme activity have been described. The aim of this study was to investigate the association of GPX1 and SOD2 genetic variants with the risk of urothelial bladder cancer (UBC) development, and to evaluate possible interactions between these genetic polymorphisms and exposure to known risk factors for UBC. Moreover, we aimed to determine whether pathological features, such as stage of disease and histological grade, were influenced by genetic polymorphisms. Furthermore, the potential prognostic role of GPX1 and SOD2 genetic variants in overall survival was evaluated in metastatic UBC patients treated with cisplatin based chemotherapy. Methods: This prospectively designed study enrolled 330 patients with urothelial bladder cancer (mean age 65 ± 10.3 years) and 227 healthy controls (mean age 63.4 ± 7.9 years). GPX1 (rs1050450) single nucleotide polymorphism was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) and SOD2 (rs4880) single nucleotide polymorphism was determined by quantitative PCR (q-PCR). In order to estimate the impact of GPX1 and SOD2 genotypes on overall survival, patients with metastatic UBC who received cisplatine based chemotherapy were followed for two years. A chi-squared test was used to analyze the genotype frequency differences between two groups. The effect of genetic polymorphisms on UBC risk was evaluated using univariate logistic regression analysis. Overall survival was evaluated using Kaplan–Meier survival analysis with the log-rank test for prognostic significance...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjecturotelijalni karcinom mokraćne bešikesr
dc.subjecturothelial bladder canceren
dc.subjectrisken
dc.subjectgenetic polymorphismsen
dc.subjectoverall survivalen
dc.subjectchemotherapyen
dc.subjectGPX1en
dc.subjectSOD2en
dc.subjectgenetski polimorfizamsr
dc.subjectukupno preživljavanjesr
dc.subjecthemioterapijasr
dc.subjectGPX1sr
dc.subjectSOD2sr
dc.titlePovezanost polimorfizma gena za glutation peroksidazu i superoksid dismutazu sa nastankom i progresijom karcinoma prelaznog epitela mokraćne bešikesr
dc.title.alternativeThe association of glutathione peroxidase and superoxide dismutase gene polymorphisms with urothelial bladder cancer development and progressionen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/9695/IzvestajKomisije18936.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/9694/Disertacija.pdf


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