Povezanost polimorfizama gena PNPLA3, NOTCH3 i EGF s pojavom hepatocelularnoga karcinoma u bolesnika s alkoholnom cirozom jetre

doctoral thesis

• Title (english): Association between the single nucleotide polymorphisms for PNPLA3, NOTCH3 and EGF with the risk of hepatocellular carcinoma occurrence in patients with alcoholic liver cirrhosis
• Author: Ana Bainrauch
• Mentor: Anna Mrzljak (mentor)
• Mentor: Tomislav Kelava (komentor)
• Committee member: Rajko Ostojić (predsjednik povjerenstva)
• Committee member: Lucija Virović Jukić (član povjerenstva)
• Committee member: Ivica Grgurević (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2024-12-17, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology
• Universal decimal classification (UDC): 612 - Physiology

Abstract

U ovom radu po prvi je puta istražen utjecaj polimorfizama gena PNPLA3 rs738409, EGF rs4444903 i NOTCH3 rs1043996 na rizik pojave hepatocelularnoga karcinoma (HCC) u hrvatskoj populaciji pacijenata transplantiranih zbog alkoholne ciroze. Uključeno je 260 bolesnika s alkoholnom cirozom od kojih 132 bez i 128 s histološki dokazanim HCC-om. Svim ispitanicima iz uzorka periferne krvi izolirana je DNK te učinjena analiza polimorfizama gena PNPLA3, EGF i NOTCH3. Rezultati pokazuju da su genotip GG za polimorfizam PNPLA3 te genotip AG i GG za polimorfizam EGF povezani s većim omjerom izgleda za pojavu HCC-a, a prisutnost G alela čimbenik je koji doprinosi povećanom riziku. Logističkom regresijom polimorfizmi PNPLA3 i EGF identificirani su kao nezavisni čimbenici rizika za pojavu HCC-a. Polimorfizam NOTCH3 gena nije statistički značajno povezan s rizikom za HCC. Kada smo analizirali povezanost polimorfizama s kliničkim pokazateljima, samo je genotip GG u usporedbi s genotipom GC/CC PNPLA3 gena bio povezan s višim vrijednostima ALT-a. Nijedan istraživan polimorfizam nije bio povezan s kliničkim i histološkim karakteristikama tumora niti s rizikom za rani recidiv HCC-a nakon transplantacije jetre.

Abstract (english)

This paper, for the first time, investigated the contribution of single nucleotide polymorphisms for PNPLA3 rs738409, EGF rs4444903 and NOTCH3 rs1043996 on the risk of hepatocellular carcinoma (HCC) in the Croatian population of patients transplanted due to alcoholic cirrhosis. The study included 260 patients with alcoholic cirrhosis, 132 without and 128 with histologically proven HCC. DNA was isolated from the peripheral blood sample of all subjects and analysis of PNPLA3, EGF and NOTCH3 polymorphisms was performed. The results show that the GG genotype for the PNPLA3 polymorphism and the AG/GG genotypes for the EGF polymorphism are associated with a higher odds ratio for the occurrence of HCC, while the presence of the G allele is a factor contributing to the risk. PNPLA3 and EGF polymorphisms were identified as independent risk factors for the occurrence of HCC. NOTCH3 polymorphism was not significantly associated with HCC risk. When we analyzed the association of polymorphisms with clinical parameters, only the GG genotype compared to the GC/CC genotype of the PNPLA3 gene was associated with higher ALT values. None of the investigated polymorphisms was associated with tumor clinical and histological characteristics or with the risk of early recurrence of HCC after liver transplantation.

• Keywords: Karcinom; hepatocelularni; Ciroza jetre; alkoholičar; Polimorfizam; jedan nukleotid; Epidermalni faktor rasta; Transplantacija jetre; Hrvatska; Neoplazme jetre; DNK
• Keywords (english): Carcinoma; Hepatocellular; Liver Cirrhosis; Alcoholic; Polymorphism; Single Nucleotide; Epidermal Growth Factor; Liver Transplantation; Croatia; Liver Neoplasms; DNA
• Language: croatian
• URN:NBN: urn:nbn:hr:105:076771
• Project: Number: UIP-2017-05-1965; Title: Uloga Notch signalnog puta u patogenezi jetrene fibroze; Title: The Role of Notch Signalling Pathway in Pathogenesis of Hepatic Fibrosis; Acronym: NOFIBRO; Leader: Tomislav Kelava; Jurisdiction: Croatia; Funder: Hrvatska zaklada za znanost; Funding stream: Installation Research Projects
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 83 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-12-19 12:41:06