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The role of pharmacogenomics of anastrazole in the interpatient variability in the intensity of adverse effects
Croatia (CroMSIC) - Josip Juraj Strossmayer University of Osijek, Osijek
J.J. Strossmayer University of Osijek, Faculty of Medicine, Department of Pharmacology
Martina Smolic, M.D., Ph.D
Kristina Bojanic,M.D., Tomislav Kizivat,M.D., Sonja Sarcevic,M.D., Nikola Raguz-Lucic,M.D.
English (German, Croatian, Serbian, Bosnian)
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Anastrozole is a selective aromatase inhibitor (AI) widely used as adjuvant treatment for early stage breast cancer. The most common adverse events associated with AIs are osteoporosis, fractures, joint symptoms, hypercholesterolemia and myalgia. Anstrazole ? related liver injury has been less frequently reported, however it can be a life-threatening side effect. Aim of this study is to elucidate how genetic polymorphism of enzymes involved in anastrazole metabolism could cause an accumulation of the anastrazole or its metabolites increasing the risk to anastrozole-induced toxicity as well as different cure rates among treated patients. Based on the results of the study a rational, individualized protocol for the treatment of patients with hormone- dependent breast cancer adapted to each patient individually would be developed.
What is the aim of the project?
Aim of the project is to elucidate genetic polymorphism of enzymes involved in anastrazole metabolism and determine the role of CYP3A4, CYP3A5 and UGT1A4 pharmacogenomics in the
interindividual variations in anastrazole metabolism and the intensity of adverse effects.
What techniques and methods are used?
Liver stiffness measurement(LSM)using transient elastography by the FibroScan (Echosens,France) and bone mineral density (BMD;g/cm2) by dual-energy x-ray absorptiometry (?Lunar Prodigy?) will be used. Genotyping of SNPs in the UGT1a4 (rs6755571), CYP3A5 (rs776746) and CYP3A4(rs2740574) genes will be performed by Taqman real-time PCR.
What is the role of the student?
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
No special requirements, no legal limitatons in the student's involvement in the project.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system
- Pharmacogenet Genomics. 2014 Dec;24(12):575-81.
- J Hum Genet. 2013 Jun;58(6):306-12. doi: 10.1038/jhg.2013.35.
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