Title Implementacija farmakogenetike za 5-fluorouracil i irinotekan u Hrvatskoj
Author Ana Begić
Mentor Nada Božina (mentor)
Committee member Karmela Barišić (predsjednik povjerenstva)
Committee member Nada Božina (član povjerenstva)
Committee member Zrinka Rajić (član povjerenstva)
Granter University of Zagreb Faculty of Pharmacy and Biochemistry Zagreb
Defense date and country 2021-09-29, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Pharmacy Pharmacy
Abstract CILJ ISTRAŽIVANJA
Cilj je ovoga specijalističkog rada prikupiti i kritički procijeniti relevantne podatke koji se
odnose na utjecaj genskih varijanti na ishode terapije 5-fluorouracilom i irinotekanom, prikazati
upute i smjernice izdane od međunarodnih tijela, te prisutne dileme u liječenju.
MATERIJALI I METODE
Za potrebe istraživanja i pisanja rada od dostupnih baza podataka pretraživane su baze podataka
Medline i PubMed prema ključnim riječima: 5-fluorouracil,
... More dihidropirimidin-dehidrogenaza,
farmakogenetika, genski polimorfizmi i irinotekan. Odabir znanstvenih članaka publiciranih u
posljednjem desetljeću obuhvaća važnije članke iz područja farmakogenetike, farmakogenomike
i farmakoterapije, starije i novije objave, originalne članke kao i preglede koji zadovoljavaju
tematiku i ciljeve istraživanja postavljene u radu.
U radu su također prikazani i podatci o implementaciji testiranja DPYD i UGT1A1 u Hrvatskoj
dobiveni u okviru doktorske disertacije dr.sc. Ivana Bilića 'Uloga polimorfizama gena
dihidropirimidin-dehidrogenaze i UDP-glukuronil-transferaze u toksičnosti kemoterapije
fluoropirimidinima i irinotekanom'. U tu svrhu prikazan je pregled rutinskih analiza pacijenata
liječenih 5-fluorouracilom i irinotekanom tijekom tri godine (2013.-2016.) u Kliničkom zavodu
za laboratorijsku dijagnostiku u Kliničkom bolničkom centru Zagreb.
RASPRAVA
Bolesnici s toksičnim nuspojavama na fluoropirimidine i irinotekan češće su nositelji
polimorfizama gena za dihidropirimidin-dehidrogenazu, između ostalih to su DPYD*2A
(c.1905+1G>A ili IVS 14+1 G>A), DPYD 496A>G (c.496A>G), te polimorfizma UGT1A1
(UGT1A1*28), u odnosu na pacijente koji nisu iskusili nuspojave. Na temelju farmakogenetičkih
analiza može se u značajnoj mjeri predvidjeti razvoj nuspojava, individualizirati, tj. prilagoditi
doza lijeka i time minimalizirati rizik od nastanka štetnih učinaka.
ZAKLJUČAK
Iako postoje jasni dokazi o vrijednosti farmakogenetičkih testiranja, njihova implementacija u
svakodnevnu kliničku praksu zaostaje za tim spoznajama. Poznavanje genskih polimorfizama ne
može apsolutno predvidjeti sve neočekivane reakcije pacijenta ali može značajno doprinijeti
individualizaciji terapije te minimalizaciji rizika. Less
Abstract (english) OBJECTIVES
The purpose of this specialist thesis is to collect and critically evaluate relevant data related to
the influence of 5-fluorouracil and irinotecan gene variants on the outcome of therapy, to present
current guidelines issued by relevant international bodies, and dilemmas in the treatment.
MATERIALS AND METHODS
For research and writing purposes, Medline and PubMed databases were searched for by
following keywords: 5-fluorouracil,
... More dihydropyrimidine-dehydrogenase, pharmacogenetics, gene
polymorphisms and irinotecan. The selection of scientific articles published in the last decade
includes the most important articles in the field of of pharmacogenetics, pharmacogenomics and
pharmacotherapy, older and newer releases, original articles and reviews that meet the topic and
goals of the research set in this thesis.
This paper presents the latest data on the implementation of DPYD and UGT1A1 testing in
Croatia obtained within the doctoral dissertation of Ivan Bilić 'The role of dihydropyrimidinedehydrogenase and UDP-glucuronyl-transferase polymorphisms in fluoropyrimidine and
irinotecan toxicity'. For this purpose, the routine analyses of patients treated with 5-fluorouracil
and irinotecan during the three years period (2013.-2016.), at the Clinical Institute for Laboratory
Diagnosis at Zagreb Clinical Hospital Center have been presented.
DISCUSSION
Patients with toxic side effects of fluoropyrimidines and irinotecan are more frequent carriers of
dihydropyrimidine-dehydrogenase genomic polymorphisms, among others DPYD*2A (1905 +
1G> A or IVS 14+1G> A), DPYD 496A> G (c.496A> G) and UGT1A1 polymorphism
(UGT1A1*28), compared to patients who do not experience side effects. Based on
pharmacogenetic analysis, it is possible to significantly anticipate the development of side
effects, to individualize, i.e. to adjust the dose of the drug and minimize the risk of side effects.
CONCLUSION
Although there is a clear evidence of pharmacogenetic testing values, the implementation in
everyday clinical practice is lagging behind these findings. Knowledge of gene polymorphisms
cannot predict all unexpected responses of the patient, but can significantly contribute to the
individualization of the therapy and minimizing the risk. Less
Keywords
5-fluorouracil
dihidropirimidin-dehidrogenaza
farmakogenetika
genski polimorfizmi
irinotekan
Keywords (english)
5-fluorouracil
dihydropyrimidine-dehydrogenase
pharmacogenetics
gene polymorphisms
irinotecan
Language croatian
URN:NBN urn:nbn:hr:163:709553
Study programme Title: Molecular diagnostics Study programme type: university Study level: postgraduate specialist Academic / professional title: sveučilišni magistar/sveučilišna magistra molekularne dijagnostike (sveučilišni magistar/sveučilišna magistra molekularne dijagnostike)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Created on 2022-03-23 16:04:26