Title Genetička podloga urođene imunosti u kroničnoj opstruktivnoj plućnoj bolesti i karcinomu pluća Title (english) Genetic background of innate immunity in COPD and lung cancer Author Irena Sokolović Mentor Marko Jakopović (mentor)Mentor Jelena Knežević (komentor)Committee member Miroslav Samaržija (predsjednik povjerenstva)Committee member Jadranka Sertić (član povjerenstva)Committee member Floriana Jakuš (član povjerenstva)Granter University of Zagreb Defense date and country 2021-09-16, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract Kronična upala povezana je sa nastankom karcinoma, a Toll-like receptori (TLR) ključni su sudionici u regulaciji upalnog odgovora. Kronična opstruktivna plućna bolest (KOPB) se smatra najvećim neovisnim čimbenikom rizika za nastanak karcinoma pluća (KP), što ukazuje da u razvoju obje bolesti postoji preklapajuća genetska podloga. Obzirom na važnu ulogu TLR-a u aktivaciji i regulaciji imunološkog odgovora, u ovom istraživanju pretpostavljeno je da bi njihova genetička varijabilnost mogla biti povezana s razvojem KOPB-a i karcinoma pluća. Rezultati ovog istraživanja pokazuju da poremećeni procesi regulacije upale, u kontekstu smanjene aktivnosti TLR-a, doprinose razvoju karcinoma pluća kod pacijenata s dijagnosticiranim KOPB-om. U istraživanje je bilo uključeno 940 pacijenata, podijeljenih u tri skupine: KOBP vs KOPB + KP, KOPB vs KP, KOPB + KP vs KP. Obuhvaćeno je 13 polimorfizama jednog nukelotida (SNP-ova) smještenih u 6 različitih gena koji kodiraju za TLR-e. Genetska povezanost procijenjena je logističkom regresijom, te je prilagođena dobi i spolu. Razina IL-6 u serumu određena je ELISA-om. Rezultati su pokazali povezanost između C/G genotipa TLR1 rs5743611 i povećanog rizika za razvoj karcinoma pluća, dok su genotipovi polimorfizama TLR5 G/G (rs2072493) i C/C (rs725084) povezani s razvojem karcinoma pluća u bolesnika sa KOBP-om. Nakon prilagodbe na dob i spol, pokazano je da je polimorfizam rs2072493 statistički značajno povezan s rizikom za razvoj karcinoma pluća u prisutnosti KOBP-a. Također, polimorfizam rs2072493 povezani je sa statistički značajnim smanjenjem koncentracije IL-6 u serumu ispitanika. Rezultati ovog istraživanja mogli bi pridonijeti razumijevanju povezanosti promijenjenog imunološkog odgovora i veze između karcinoma pluća i KOBP-a. Također, ovi bi rezultati možda mogli predstavljati u literaturi još neopisanu, novu povezanost između karcinoma pluća i KOBP-a u kontekstu promijenjenog imunološkog odgovora, a koja bi mogla omogućiti predviđanje rizika za razvoj bolesti, bolje razumijevanje mehanizama nastanka bolesti i razvoj novih strategija u liječenju ovih teških bolesti.
Abstract (english) Chronic inflammation is associated with cancer development, and Toll-like receptors (TLRs) are key participants in the regulation of the inflammatory response. Chronic obstructive pulmonary disease (COPD) is considered to be the largest independent risk factor for lung cancer (LC), indicating there is an overlapping genetic background in the development of both diseases. Given the important role of TLRs in the activation and regulation of the immune response, it was hypothesized in this study that their genetic variability could be associated with the development of COPD and lung cancer. The results of this study show that impaired inflammatory regulation processes, in the context of decreased TLR activity, contribute to the development of lung cancer in patients diagnosed with COPD. The study included 940 patients, divided into three groups: COPD vs COPD + KP, COPD vs KP, COPD + KP vs KP. It included 13 polymorphisms of one nucleotide (SNP) located in 6 different genes encoding TLRs. Genetic associations were estimated using logistic regression and adjusted for age and gender. Serum IL-6 levels were determined by ELISA. The results showed an association between C/G genotype TLR1 rs5743611 and an increased risk of developing lung cancer, while G/G genotype of TLR5 rs2072493 and C/C genotype of TLR5 rs725084 polymorphism were associated with the development of lung cancer in patients with COPD. After age and gender adjustment, the TLR5 rs2072493 polymorphism showed statistically significant association with risk of lung cancer development in the presence of COPD. Also, the rs2072493 polymorphism was associated with a statistically significant decrease in the serum IL-6 concentration. The results of this study could contribute to an understanding of the association between altered immune response and the link between lung cancer and COPD. Also, these results might represent an as yet undescribed, new association between lung cancer and COPD in the context of altered immune response, which could also allow risk prediction, better understanding of disease mechanisms and development of new strategies in the treatment of these serious diseases.
Keywords
Toll-Like Receptor 1
Toll-Like Receptor 5
Nukleotidi
Plućna bolest
kronična opstrukcija
Neoplazme pluća
Polimorfizam
genetski
Genotip
Genetska pozadina
Faktori rizika
Enzimski imunološki test
Imunitet
Upala
Keywords (english)
Toll-Like Receptor 1
Toll-Like Receptor 5
Nucleotides
Pulmonary Disease
Chronic Obstructive
Lung Neoplasms
Polymorphism
Genetic
Genotype
Genetic Background
Risk Factors
Enzyme-Linked Immunosorbent Assay
Immunity
Inflammation
Language croatian URN:NBN urn:nbn:hr:105:567748 Study programme Title: Biomedicine and Health Sciences Type of resource Text Extent 104 str. File origin Born digital Access conditions Open access Terms of use Created on 2021-12-02 10:00:36
