Utjecaj polimorfizma gena HER-2/neu na kardiotoksičnost uzrokovanu monoklonskim protutijelom trastuzumabom

doctoral thesis

• Title (english): Influence of HER-2/neu gene polymorphism on monoclonal antibody trastuzumab induced cardiotoxicity
• Author: Ljubica Vazdar
• Mentor: Hrvoje Pintarić (mentor); MBZ: 224771
• Committee member: Sonja Levanat (predsjednik povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; Zagreb
• Defense date and country: 2017, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

Malobrojna dosadašnja istraživanja pokazala su dvojbene rezultate utjecaja polimorfizma gena HER-2/neu na kardiotoksičnost uzrokovanu monoklonskim protutijelom trastuzumabom. Obzirom na izuzetno važan biljeg u onkologiji i mogući čimbenik rizika srčanog oštećenja, nametnula se potreba ovakvog istraživanja. U istraživanje su uključene ispitanice adjuvantno liječene trastuzumabom zbog HER2 pozitivnog ranog raka dojke (n=177). Ispitanice su podijeljenje u dvije grupe: grupa A (n=99) kod kojih nije došlo do kardiotoksičnosti tijekom liječenja trastuzumabom i grupa B (n=78) kod kojih je došlo do razvoja kardiotoksičnosti. Istraženi su rizični čimbenici kao i osobitosti same kardiotoksičnosti, vrijeme pojavnosti i oporavka te reverzibilnost. Svim ispitanicama je lančanom reakcijom polimeraze određen polimorfizam gena HER-2/neu na kodonu 655 [Ile655Val] te distribucija genotipa Ile/Val, Ile/Ile i Val/Val. Praćenje srčane funkcije ehokardiografijom bilo je u skladu s usvojenim smjernicama praćenja. Iz rezultata dobivenih usporedbom grupa A i B nije nađena povezanost između pojedinog genotipa HER-2/neu i pojave kardiotoksičnosti.

Abstract (english)

A few studies so far have shown doubtful results on influence of HER-2/ neu gene polymorphism on cardiotoxicity caused by monoclonal antibody trastuzumab. Remarkable importance of this marker in oncology and its place as a possible risk factor for cardial damage, imposed the need for this kind of research. The study included patients adjuvantly treated with trastuzumab for HER2 positive breast cancer (n = 177). Subjects were divided into two groups: group A (n = 99), which did not experience cardiotoxicity during treatment with trastuzumab and group B (n = 78) which did. Risk factors were investigated as well as the characteristics of cardiotoxicity, time of occurrence and recovery, and reversibility. Polymorphism of the HER-2/ neu gene on codon 655 [Ile655Val] and Ile/Val, Ile/Ile and Val/Val genotype distribution was determined by polimerase chain reaction in all patients. Heart function monitoring with echocardiography was consistent with the adopted monitoring guidelines. From the results obtained by comparing groups A and B, no correlation was found between HER-2/neu genotype and cardiotoxicity.

• Keywords: polimorfizam; HER-2/neu; trastuzumab; kardiotoksičnost
• Keywords (english): polymorphism; HER-2/neu; trastuzumab; cardiotoxicity
• Language: croatian
• URN:NBN: urn:nbn:hr:217:505019
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-11-02 12:41:43