Dihydropyrimidine Dehydrogenase Polymorphism c.2194G>A Screening Is a Useful Tool for Decreasing Gastrointestinal and Hematological Adverse Drug Reaction Risk in Fluoropyrimidine-Treated Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patients
2.2. Statistical Analysis
3. Results
3.1. Characteristics of Patient Candidates for Fluoropyrimidine Therapies
3.2. Analysis of DPYD Polymorphisms in the Cohort
Variant | rsID | Nucleotide Change | Amino Acid Change | Dpd Activity | DPYD Carriers (n) (%) | Suggested Dose (5-FU/ Capecitabine etc.) | Allele Frequency Reported in gnomAD | Allele Frequency Observed in the Cohort |
---|---|---|---|---|---|---|---|---|
*6 | rs1801160 | c.2194G>A | (p.Val732Ile) | Normal function | 26 (19.70%) | 100% ab initio, 85% in case of toxicity | 0.04675 | 0.065 |
3.3. Reported ADRs after Fluoropyrimidines Treatment in Carrier Patients of WT and DPYD*6
ADRs Gastrointestinal (76.5%) | Grade ≥ 2 |
---|---|
Nausea/Vomiting | 24 (18.18%) |
Diarrhea | 56 (42.41%) |
Stomatitis | 21 (15.91%) |
ADRs Dermatological (8.33%) | Grade ≥ 2 |
Hand–foot syndrome | 11 (8.33%) |
ADRs Hematological (52.27%) | Grade ≥ 3 |
Fever | 6 (4.55%) |
Leucopenia | 19 (14.39%) |
Neutropenia | 28 (21.21%) |
Anemia | 7 (5.30%) |
Thrombocytopenia | 9 (6.82%) |
ADRs Neurological (2.94%) | |
Peripheral neuropathy | 4 (2.94%) |
3.4. Assessment of ADRs between Patients with Mutated DPYD*6 and WT Stratifying by Gender
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Cohort |
---|---|
Patients | 132 |
Gender (M/F) | 72/60 |
Age (years) | 66.5 ± 10.4 |
Ancestry | Caucasian, European |
Colorectal cancer | 91 (68.94%) |
Gastric cancer | 37 (28.03%) |
Breast cancer | 4 (3.03%) |
Treatment | |
FU-LV (De Gramont regimen) | 6 (4.5%) |
5-FU | 3 (2.3%) |
FOLFOX | 90 (68.2%) |
FOLFIRI | 14 (10.6%) |
FOLFIRINOX | 15 (11.4%) |
Capecitabine | 4 (3%) |
Combination with immunotherapy | |
Yes | 30 (22.7%) |
No | 102 (77.3%) |
Comorbidity | 34 (25.75%) |
No Comorbidity | 98 (74.25%) |
Side Effect | WT (n = 106) | DPYD*6 Polymorphism c.2194G>A (n = 26) | p-Value |
---|---|---|---|
ADRs—Gastrointestinal | |||
Nausea/Vomiting (24 cases) | 14/106 | 10/26 | p = 0.002 |
Diarrhea (56 cases) | 32/106 | 24/26 | p < 0.001 |
Stomatitis (21 cases) | 15/106 | 6/26 | p = 0.03 |
ADRs—Dermatological | |||
Hand–foot syndrome (11 cases) | 8/106 | 3/26 | p = 0.45 |
ADRs—Hematological | |||
Fever (6 cases) | 3/106 | 3/26 | p = 0.09 |
Leucopenia (19 cases) | 9/106 | 10/26 | p < 0.001 |
Neutropenia (28 cases) | 16/106 | 12/26 | p = 0.002 |
Anemia (7 cases) | 5/106 | 2/26 | p = 0.62 |
Thrombocytopenia (9 cases) | 4/106 | 5/26 | p = 0.01 |
ADRs—Neurological | |||
Peripheral Neuropathy (4 cases) | 2/106 | 2/26 | p = 0.17 |
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Ardizzone, A.; Bulzomì, M.; De Luca, F.; Silvestris, N.; Esposito, E.; Capra, A.P. Dihydropyrimidine Dehydrogenase Polymorphism c.2194G>A Screening Is a Useful Tool for Decreasing Gastrointestinal and Hematological Adverse Drug Reaction Risk in Fluoropyrimidine-Treated Patients. Curr. Issues Mol. Biol. 2024, 46, 9831-9843. https://doi.org/10.3390/cimb46090584
Ardizzone A, Bulzomì M, De Luca F, Silvestris N, Esposito E, Capra AP. Dihydropyrimidine Dehydrogenase Polymorphism c.2194G>A Screening Is a Useful Tool for Decreasing Gastrointestinal and Hematological Adverse Drug Reaction Risk in Fluoropyrimidine-Treated Patients. Current Issues in Molecular Biology. 2024; 46(9):9831-9843. https://doi.org/10.3390/cimb46090584
Chicago/Turabian StyleArdizzone, Alessio, Maria Bulzomì, Fabiola De Luca, Nicola Silvestris, Emanuela Esposito, and Anna Paola Capra. 2024. "Dihydropyrimidine Dehydrogenase Polymorphism c.2194G>A Screening Is a Useful Tool for Decreasing Gastrointestinal and Hematological Adverse Drug Reaction Risk in Fluoropyrimidine-Treated Patients" Current Issues in Molecular Biology 46, no. 9: 9831-9843. https://doi.org/10.3390/cimb46090584