Association Between DPYD Gene Variants and Severe Fluoropyrimidine-Related Toxicity in Asian and African Populations: A Systematic Review.
4 affiliations
- 1Department of Microbiology and Laboratory Sciences, Faculty of Medicine and Health Sciences, SIMAD University, Mogadishu, Somalia.
- 2Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
- 3Faculty of Medicine and Health Sciences, SIMAD University, Mogadishu, Somalia.
- 4Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand.
Abstract
Introduction
Fluoropyrimidines are widely used against solid tumors, and severe treatment-related toxicity remains a major clinical problem. DPYD variants prioritized in predominantly European guidelines may not capture those most relevant elsewhere, and their predictive value in Asian and African study populations is unclear.Methods
We searched PubMed, Embase, Scopus, the Cochrane Library, and Google Scholar. Eligible studies reported DPYD variants with toxicity outcomes in Asian or African study populations receiving fluoropyrimidine-based chemotherapy. The risk of bias was assessed using the design-specific Joanna Briggs Institute tools, and findings were synthesized narratively by variant, following the PRISMA 2020.Results
Twenty-three studies published between 2007 and 2025, spanning 14 countries, were included, six at low risk of bias, nine at moderate, and eight at high. Recurrent variants were c.1627A>G (DPYD*5), c.85T>C (DPYD*9A), c.1905+1G>A (DPYD*2A), c.496A>G, c.1896T>C, and c.2194G>A (DPYD*6). Associations were most consistent for c.85T>C, with unadjusted odds ratios of 2.3 for hand-foot syndrome and 2.7 for diarrhea in South India, and an adjusted odds ratio of 4.35 for mucositis in Tunisia, all for any-grade toxicity. For c.1905+1G>A, adjusted odds ratios were 6.47 for grade 3-4 neutropenia and 5.76 for diarrhea in Bangladesh. Findings for c.1627A>G were inconsistent in direction. Only one study corrected for multiple testing, and the designs, regimens, grading systems, and genotyping platforms were highly heterogeneous.Conclusion
Evidence for population-specific DPYD variation is strongest in Asian populations. Data from the African populations represented in the available studies, confined to Tunisia, Algeria, Sudan, and Zimbabwe, are too sparse for strong conclusions. No carrier of the four guideline variants was found among 150 genotyped Zimbabwean patients, yet 36% of the 50 who received fluoropyrimidine had severe adverse events. Harmonized prospective studies reporting genotype-specific numerators and denominators are needed before population-specific variants can be considered clinically actionable.
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BibTeX
@article{abdi2026association,
title = {{Association Between DPYD Gene Variants and Severe Fluoropyrimidine-Related Toxicity in Asian and African Populations: A Systematic Review.}},
author = {Abdkerem Abdulahi Abdi and Mohamed Mustaf Ahmed and Chalirmporn Atasilp and Abdinasir Mohamed Aray and Chonlaphat Sukasem},
journal = {Pharmacogenomics and personalized medicine},
year = {2026},
month = oct,
doi = {10.2147/pgpm.s641214},
url = {https://europepmc.org/article/MED/42921530},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Association Between DPYD Gene Variants and Severe Fluoropyrimidine-Related Toxicity in Asian and African Populations: A Systematic Review.
AU - Abdkerem Abdulahi Abdi
AU - Mohamed Mustaf Ahmed
AU - Chalirmporn Atasilp
AU - Abdinasir Mohamed Aray
AU - Chonlaphat Sukasem
PY - 2026
DA - 2026/10/19
JO - Pharmacogenomics and personalized medicine
DO - 10.2147/pgpm.s641214
UR - https://europepmc.org/article/MED/42921530
AB - Introduction Fluoropyrimidines are widely used against solid tumors, and severe treatment-related toxicity remains a major clinical problem. DPYD variants prioritized in predominantly European guidelines may not capture those most relevant elsewhere, and their predictive value in Asian and African study populations is unclear.Methods We searched PubMed, Embase, Scopus, the Cochrane Library, and Google Scholar. Eligible studies reported DPYD variants with toxicity outcomes in Asian or African study populations receiving fluoropyrimidine-based chemotherapy. The risk of bias was assessed using the design-specific Joanna Briggs Institute tools, and findings were synthesized narratively by variant, following the PRISMA 2020.Results Twenty-three studies published between 2007 and 2025, spanning 14 countries, were included, six at low risk of bias, nine at moderate, and eight at high. Recurrent variants were c.1627A>G (DPYD*5), c.85T>C (DPYD*9A), c.1905+1G>A (DPYD*2A), c.496A>G, c.1896T>C, and c.2194G>A (DPYD*6). Associations were most consistent for c.85T>C, with unadjusted odds ratios of 2.3 for hand-foot syndrome and 2.7 for diarrhea in South India, and an adjusted odds ratio of 4.35 for mucositis in Tunisia, all for any-grade toxicity. For c.1905+1G>A, adjusted odds ratios were 6.47 for grade 3-4 neutropenia and 5.76 for diarrhea in Bangladesh. Findings for c.1627A>G were inconsistent in direction. Only one study corrected for multiple testing, and the designs, regimens, grading systems, and genotyping platforms were highly heterogeneous.Conclusion Evidence for population-specific DPYD variation is strongest in Asian populations. Data from the African populations represented in the available studies, confined to Tunisia, Algeria, Sudan, and Zimbabwe, are too sparse for strong conclusions. No carrier of the four guideline variants was found among 150 genotyped Zimbabwean patients, yet 36% of the 50 who received fluoropyrimidine had severe adverse events. Harmonized prospective studies reporting genotype-specific numerators and denominators are needed before population-specific variants can be considered clinically actionable.
SN - 1178-7066
ER -