Precision Medicine in Childhood Cancer: The Influence of Genetic Polymorphisms on Vincristine-Induced Peripheral Neuropathy
Abstract
:1. Introduction
2. Results
2.1. Sociodemographic and Clinicopathologic Characteristics
2.2. Genotype Distribution
2.3. Influence of Clinicopathologic and Genetic Variables on Peripheral Neuropathy in Pediatric Cancer Patients Treated with Vincristine
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Study Population
4.3. Ethics Statements
4.4. Sociodemographic and Clinicopathologic Data
4.5. Genetic Variables
4.5.1. DNA Isolation
4.5.2. Detection of Gene Polymorphisms
- (1)
- Rate of missing genotypes per SNP < 0.05.
- (2)
- MAF > 0.01.
- (3)
- p-value > 0.05 in the HWE test.
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Variable | n | % | Median (p25–p75) |
---|---|---|---|
Sex | |||
Female | 42 | 47.73 | |
Male | 46 | 52.27 | |
Family history of cancer | |||
Yes | 45 | 51.14 | |
No | 43 | 48.86 | |
Disease | |||
Acute lymphocytic leukemia | 49 | 55.68 | |
Non-Hodgkin lymphoma | 15 | 17.05 | |
Ewing sarcoma | 7 | 7.95 | |
Hodgkin lymphoma | 6 | 6.82 | |
Ependymoma | 4 | 4.55 | |
Other cancers | 7 | 7.95 | |
Age at diagnosis | 6 (3–9) | ||
Neurotoxicity | |||
Yes | 10 | 11.36 | |
No | 78 | 88.64 | |
Peripheral Neuropathy | |||
Yes | 8 | 9.09 | |
No | 80 | 90.91 |
Characteristics | N | Peripheral Neuropathy | p-Value | OR | 95% CI | |
---|---|---|---|---|---|---|
No n (%) | Yes n (%) | |||||
Gender | ||||||
Female | 42 | 36 (85.7) | 6 (14.3) | 0.144 * | ||
Male | 46 | 44 (95.7) | 2 (4.3) | |||
Family history of cancer | ||||||
No | 43 | 39 (90.7) | 4 (9.3) | 0.951 * | ||
Yes | 45 | 41 (91.1) | 4 (8.9) | |||
Disease | ||||||
Acute lymphocytic leukemia | 49 | 46 (93.9) | 3 (6.1) | 0.051 * | 1 | |
Non-Hodgkin lymphoma | 15 | 14 (93.3) | 1 (6.7) | 1.10 | 0.05–9.35 | |
Other cancers | 7 | 7 (100.0) | 0 (0.0) | 1.30 × 10−7 | NA-9.49 × 10139 | |
Ewing sarcoma | 7 | 6 (85.7) | 1 (14.3) | 2.56 | 0.12–24.08 | |
Hodgkin lymphoma | 6 | 3 (50.0) | 3 (50.0) | 15.33 | 2.11–126.49 | |
Ependymoma | 4 | 4 (100.0) | 0 (0.0) | 1.30 × 10−7 | NA-1.60 × 10187 | |
Age at diagnosis | 88 | 6 (3.0–8.0) | 9 (7.0–13.25) | 0.029 | 1.22 | 1.03–1.50 |
Gene | SNP | Genotype | N | Peripheral Neuropathy | p-Value | Ref | OR | 95% CI | |
---|---|---|---|---|---|---|---|---|---|
No n (%) | Yes n (%) | ||||||||
ABCB1 | rs1128503 | AA | 23 | 21 (91.3) | 2 (8.7) | 0.575 * | |||
AG | 39 | 34 (87.2) | 5 (12.8) | ||||||
GG | 26 | 25 (96.2) | 1 (3.8) | ||||||
A | 62 | 55 (88.7) | 7 (11.3) | 0.427 * | |||||
G | 65 | 59 (90.8) | 6 (9.2) | 1 * | |||||
ABCC1 | rs246240 | AA | 68 | 65 (95.6) | 3 (4.4) | 0.004 * | AA | 1 | |
AG | 19 | 15 (78.9) | 4 (21.1) | 5.78 | 1.16–32.03 | ||||
GG | 1 | 0 (0.0) | 1 (100.0) | 3.39 × 108 | 2.37–NA | ||||
A | 87 | 80 (92.0) | 7 (8.0) | 0.090 * | |||||
G | 20 | 15 (75.0) | 5 (25.0) | 0.013 * | AA | 7.00 | 1.21–50.19 | ||
ABCC2 | rs717620 | CC | 45 | 41 (91.1) | 4 (8.9) | 0.669 * | |||
CT | 33 | 29 (87.9) | 4 (12.1) | ||||||
TT | 10 | 10 (100.0) | (0.0) | ||||||
C | 78 | 70 (89.7) | 8 (10.3) | 0.589 * | |||||
T | 43 | 39 (90.7) | 4 (9.3) | 1 * | |||||
CEP72 | rs924607 | CC | 28 | 26 (92.9) | 2 (7.1) | 0.883 * | |||
CT | 46 | 41 (89.1) | 5 (10.9) | ||||||
TT | 14 | 13 (92.9) | 1 (7.1) | ||||||
C | 74 | 67 (90.5) | 7 (9.5) | 1 * | |||||
T | 60 | 54 (90.0) | 6 (10.0) | 1 * |
Characteristics | Peripheral Neuropathy * | |||
---|---|---|---|---|
p-Value | q-Value | OR | 95% CI | |
ABCC1 rs246240 (G vs. AA) | 0.006 | 0.025 | 12.45 | 2.26–100.42 |
Age at diagnosis | 0.016 | 0.050 | 1.33 | 1.07–1.75 |
Gene | SNP | dbSNP ID | Assay ID |
---|---|---|---|
ABCB1 | A > G | rs1128503 | C___7586662_10 |
ABCC1 | A > G | rs246240 | C___1003698_10 |
ABCC2 | C > T | rs717620 | C___2814642_10 |
CEP72 | C > T | rs924607 | C___8292459_20 |
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Marangoni-Iglecias, L.; Rojo-Tolosa, S.; Márquez-Pete, N.; Cura, Y.; Moreno-Toro, N.; Membrive-Jiménez, C.; Sánchez-Martin, A.; Pérez-Ramírez, C.; Jiménez-Morales, A. Precision Medicine in Childhood Cancer: The Influence of Genetic Polymorphisms on Vincristine-Induced Peripheral Neuropathy. Int. J. Mol. Sci. 2024, 25, 8797. https://doi.org/10.3390/ijms25168797
Marangoni-Iglecias L, Rojo-Tolosa S, Márquez-Pete N, Cura Y, Moreno-Toro N, Membrive-Jiménez C, Sánchez-Martin A, Pérez-Ramírez C, Jiménez-Morales A. Precision Medicine in Childhood Cancer: The Influence of Genetic Polymorphisms on Vincristine-Induced Peripheral Neuropathy. International Journal of Molecular Sciences. 2024; 25(16):8797. https://doi.org/10.3390/ijms25168797
Chicago/Turabian StyleMarangoni-Iglecias, Luciana, Susana Rojo-Tolosa, Noelia Márquez-Pete, Yasmín Cura, Noelia Moreno-Toro, Cristina Membrive-Jiménez, Almudena Sánchez-Martin, Cristina Pérez-Ramírez, and Alberto Jiménez-Morales. 2024. "Precision Medicine in Childhood Cancer: The Influence of Genetic Polymorphisms on Vincristine-Induced Peripheral Neuropathy" International Journal of Molecular Sciences 25, no. 16: 8797. https://doi.org/10.3390/ijms25168797