PMID- 37108974
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230501
IS  - 2075-4426 (Print)
IS  - 2075-4426 (Electronic)
IS  - 2075-4426 (Linking)
VI  - 13
IP  - 4
DP  - 2023 Mar 28
TI  - Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of 
      Cancer Patients on Standard of Care Treatment in Zimbabwe.
LID - 10.3390/jpm13040588 [doi]
LID - 588
AB  - Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They 
      are, however, associated with adverse events (AEs), of which gastrointestinal, 
      myelosuppression and palmar-plantar erythrodysesthesia are the most common. 
      Clinical guidelines are used for fluoropyrimidine dosing based on 
      dihydropyrimidine dehydrogenase (DPYD) genetic polymorphism and have been shown 
      to reduce these AEs in patients of European ancestry. This study aimed to 
      evaluate, for the first time, the clinical applicability of these guidelines in a 
      cohort of cancer patients on fluoropyrimidine standard of care treatment in 
      Zimbabwe. DNA was extracted from whole blood and used for DPYD genotyping. 
      Adverse events were monitored for six months using the Common Terminology 
      Criteria for AEs (CTCAE) v.5.0. None of the 150 genotyped patients was a carrier 
      of any of the pathogenic variants (DPYD*2A, DPYD*13, rs67376798, or rs75017182). 
      However, severe AEs were high (36%) compared to those reported in the literature 
      from other populations. There was a statistically significant association between 
      BSA (p = 0.0074) and BMI (p = 0.0001) with severe global AEs. This study has 
      shown the absence of the currently known actionable DPYD variants in the 
      Zimbabwean cancer patient cohort. Therefore, the current pathogenic variants in 
      the guidelines might not be feasible for all populations hence the call for 
      modification of the current DPYD guidelines to include minority populations for 
      the benefit of all diverse patients.
FAU - Afolabi, Boluwatife Lawrence
AU  - Afolabi BL
AUID- ORCID: 0000-0002-4211-0254
AD  - African Institute of Biomedical Science and Technology, Harare P.O. Box 2294, 
      Zimbabwe.
AD  - Department of Biotechnology, School of Health Sciences, Chinhoyi University of 
      Technology, Chinhoyi Private Bag 7724, Zimbabwe.
FAU - Mazhindu, Tinashe
AU  - Mazhindu T
AUID- ORCID: 0000-0003-3446-3049
AD  - African Institute of Biomedical Science and Technology, Harare P.O. Box 2294, 
      Zimbabwe.
AD  - Department of Oncology, Faculty of Medicine and Health Sciences, University of 
      Zimbabwe, Harare P.O. Box 2294, Zimbabwe.
FAU - Zedias, Chikwambi
AU  - Zedias C
AUID- ORCID: 0000-0002-8638-6236
AD  - African Institute of Biomedical Science and Technology, Harare P.O. Box 2294, 
      Zimbabwe.
AD  - Department of Biotechnology, School of Health Sciences, Chinhoyi University of 
      Technology, Chinhoyi Private Bag 7724, Zimbabwe.
FAU - Borok, Margaret
AU  - Borok M
AD  - Department of Oncology, Faculty of Medicine and Health Sciences, University of 
      Zimbabwe, Harare P.O. Box 2294, Zimbabwe.
FAU - Ndlovu, Ntokozo
AU  - Ndlovu N
AD  - Department of Oncology, Faculty of Medicine and Health Sciences, University of 
      Zimbabwe, Harare P.O. Box 2294, Zimbabwe.
FAU - Masimirembwa, Collen
AU  - Masimirembwa C
AD  - African Institute of Biomedical Science and Technology, Harare P.O. Box 2294, 
      Zimbabwe.
FAU - On Behalf Of Consortium For Genomics And Therapeutics In Africa Cgta
AU  - On Behalf Of Consortium For Genomics And Therapeutics In Africa Cgta
LA  - eng
GR  - INV-036801/GATES/Bill & Melinda Gates Foundation/United States
GR  - 5P20CA210677/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20230328
PL  - Switzerland
TA  - J Pers Med
JT  - Journal of personalized medicine
JID - 101602269
PMC - PMC10141018
OTO - NOTNLM
OT  - adverse drug reactions
OT  - cancer
OT  - capecitabine
OT  - fluorouracil
OT  - genetic polymorphism
OT  - precision medicine
COIS- The funders had no role in the design of the study; in the collection, analyses, 
      or interpretation of data; in the writing of the manuscript; or in the decision 
      to publish the results.
EDAT- 2023/04/28 06:42
MHDA- 2023/04/28 06:43
PMCR- 2023/03/28
CRDT- 2023/04/28 01:31
PHST- 2023/02/10 00:00 [received]
PHST- 2023/03/20 00:00 [revised]
PHST- 2023/03/21 00:00 [accepted]
PHST- 2023/04/28 06:43 [medline]
PHST- 2023/04/28 06:42 [pubmed]
PHST- 2023/04/28 01:31 [entrez]
PHST- 2023/03/28 00:00 [pmc-release]
AID - jpm13040588 [pii]
AID - jpm-13-00588 [pii]
AID - 10.3390/jpm13040588 [doi]
PST - epublish
SO  - J Pers Med. 2023 Mar 28;13(4):588. doi: 10.3390/jpm13040588.