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Određivanje polimorfizama gena za glutation transferazu i biohemijskih markera kod bolesnika sa kolorektalnim karcinomom

Determination of glutathione transferase genetic polymorphisms and biochemical markers in colorectal cancer patients

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Author
Stojković-Lalošević
Mentor
Krivokapić, Zoran
Committee members
Pavlović-Marković, Aleksandra
Plješa-Ercegovac, Marija
Simić, Tatjana
Barišić, Goran
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Abstract
Kolorektalni karcinom (KRK) je drugi najčešći karcinom u opštoj populaciji, posle karcinoma pluća kod muškaraca i karcinoma dojke kod žena. Glutation transferaze (GST) su familija enzima koji su uključeni u proces detoksikacije heterocikličnih amina i policikličnih aromatičnih ugljovodonika, koji su prepoznati faktori rizika u razvoju KRK. Polimorfizmi GST često dovode do potpunog odsustva ili izmenjene enzimske aktivnosti, što može imati efekat na nastanak KRK-a. Pored ranog otkrivanja, prepoznavanja faktora rizika, u svakodnevnoj kliničkoj praksi od velikog je značaja i pravovremena procena stadijuma bolesti. U proceni stadijuma bolesti kao i u kliničkom praćenju bolesnika, različiti biohemijski markeri i parametri sistemske inflamacije svakodnevno se koriste. Cilj Cilj istraživanja bio je da se ispita uticaj genskog polimorfizma gena za GST na rizik za nastanak KRK, moguća povezanost između polimorfizma gena za GST i biohemijskih i fenotipskih karakteristika tumora, uključujući tip,... stadijum i gradus KRK, kao i ispitivanje potencijalnog prognostičkog značaja GST kod bolesnika sa KRK. Pored toga, cilj istraživanja bio je ispitivanje dijagnostičke efikasnosti preoperativnih vrednosti karcinoembriogenog antigena (CEA) kao i karbohidratnog antigena (CA 19-9) kao i parametara sistemske inflamacije u proceni stadijuma bolesti. Materijal i metode U istraživanje je bilo uključeno 523 bolesnika sa histopatološki potvrđenom dijagnozom kolorektalnog karcinoma koji su lečeni na Klinici za digestivnu hirurgiju - Prva hirurška klinika Kliničkog centra Srbije u Beogradu, dok je kontrolnu grupu činilo 400 po uzrastu (± 2 godine) i polu uparenih ispitanika, bez verifikovanog malignog oboljenja. Prisustvo delecionih polimorfizama GSTM1 i GSTT1 ispitivano je PCR (engl. polymerase chain reaction) metodom. Pojedinačni nukleotidni polimorfizmi GST A1 i P1 ispitivani su RFLP (eng. restriction fragment length polymorphism) metodom. Biohemijski markeri određivani su elektrohemiluminescentnom analizom (ECL), dok su parametri sistemske inflamacije određivani električnom impedancom (Coulter princip)...

Introduction Glutathione transferases (GSTs) are xenobiotic-conjugating enzymes involved in the detoxification of both heterocyclic aromatic amines and polycyclic aromatic hydrocarbons, widely recognized risk factors for colorectal cancer (CRC) development. Polymorphisms in GSTs often lead to alteration or complete lack of enzyme activity, which might have an effect on CRC carcinogenesis. Adequate diagnosis of CRC development and progression is of great importance. Hence in everyday clinical practice biochemical markes as well as parameters of systemic infllamtaion are often used. Aim The aim of this study was to investigate GST gene variants as risk factors in patients with CRC, as well as to investigate biochemical markers and parameters of systemic inflammation as tools for assessment of tumor characteristics in newly diagnosed CRC patients. Material and methods A total of 523 CRC patients administered for surgical resection and 400 matched controls were included. Deletion polymorph...isms of GSTM1 and GSTT1 were investigated by polymerase chain reaction. Single nucleotide polymorphisms of GST A1 and GSTP1 were investigated by restriction fragment length polymorphism method. Biochemical markers were investigated with ellectrochemiluminesce, whereas electric impedance was used for assessment of parameters of systemic inflammation. Results The association between GST genotype and risk of CRC development was found in carriers of GSTT1-null and GSTP1-variant genotypes individually (p = 0.050 and p=0.016, respectively). Furthermore, statistically significant association was found when combination of GSTP1-variant genotype with any of other three common GST genotypes was analyzed with respect to CRC susceptibility...

Faculty:
Универзитет у Београду, Медицински факултет
Date:
16-09-2020
Keywords:
glutation transferaze / glutathione transferases / polymorphism / colorectal cancer, carcinogenesis / biochemical markers / CA 19-9 / CEA / systemic inflammation / polimorfizmi / kolorektalni karcinom, karcinogeneza / biohemijski markeri / CA 19-9 / CEA / sistemska inflamacija
[ Google Scholar ]
Handle
https://hdl.handle.net/21.15107/rcub_nardus_18261
URI
http://eteze.bg.ac.rs/application/showtheses?thesesId=8087
https://fedorabg.bg.ac.rs/fedora/get/o:23583/bdef:Content/download
http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=37136649
https://nardus.mpn.gov.rs/handle/123456789/18261

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