SynthesisPharmacogenetics and genomics2017
TPMT, COMT and ACYP2 genetic variants in paediatric cancer patients with cisplatin-induced ototoxicity.
Synthesis in Pharmacogenetics and genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 3 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 3 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Long-term cisplatin nephrotoxicity after childhood cancer: a systematic review and meta-analysis.Pediatric nephrology (Berlin, Germany) · 2024Pooled it
- Pharmacogenetics of chemotherapy treatment response and -toxicities in patients with osteosarcoma: a systematic review.BMC cancer · 2022Pooled it
- The genetic vulnerability to cisplatin ototoxicity: a systematic review.Scientific reports · 2019Pooled it
- Inherited immune traits and cisplatin-induced ototoxicity in cancer patients: a Mendelian randomization study.International journal of clinical pharmacy · 2026Article
- ACYP2 Induces Temozolomide Resistance in Glioblastoma by Promoting PARP1-Mediated DNA Damage Repair.Molecular cancer research : MCR · 2026Article
- From Ototoxicity to Otoprotection: Mechanism and Protective Strategies in Cisplatin Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Ototoxicity in Cancer Therapies.Oral diseases · 2025Review
- Development and Validation of a Novel Prediction Model for Hearing Loss From Cisplatin Chemotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- The Role of Genetic and Non-Genetic Factors in the Occurrence of Cisplatin-Associated Ototoxicity.International journal of molecular sciences · 2025Review
- Cisplatin-Induced Hearing Loss, Oxidative Stress, and Antioxidants as a Therapeutic Strategy-A State-of-the-Art Review.Antioxidants (Basel, Switzerland) · 2024Review
- Leveraging large-scale datasets and single cell omics data to develop a polygenic score for cisplatin-induced ototoxicity.Human genomics · 2024Article
- The role of genetic variants in the prediction of hearing loss due to cisplatin chemoradiotherapy.Cancer medicine · 2024Article
- Genetic predictors of neurocognitive outcomes in survivors of pediatric brain tumors.Journal of neuro-oncology · 2023Article
- Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy.International journal of molecular sciences · 2023Article
- Advancing Precision Medicine in Paediatrics: Past, present and future.Cambridge prisms. Precision medicine · 2023Review
- A Missense Variant inBiomedicines · 2022Article
- Modern developments in germline pharmacogenomics for oncology prescribing.CA: a cancer journal for clinicians · 2022Review
- Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans.Disease models & mechanisms · 2022Article
- Article
Corrections and comments
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Authors and funding
17 authors at 11 institutions in 3 countries.
Funding
Abstract
objectivesCisplatin ototoxicity affects 42-88% of treated children. Catechol-O-methyltransferase (COMT), thiopurine methyltransferase (TPMT) and AYCP2 genetic variants have been associated with ototoxicity, but the findings have been contradictory. The aims of the study were as follows: (a) to investigate these associations in a carefully phenotyped cohort of UK children and (b) to perform a systematic review and meta-analysis.
methodsWe recruited 149 children from seven UK centres using a retrospective cohort study design. All participants were clinically phenotyped carefully. Genotyping was performed for one ACYP2 (rs1872328), three TPMT (rs12201199, rs1142345 and rs1800460) and two COMT (rs4646316 and rs9332377) variants.
resultsFor CTCAE grading, hearing loss was present in 91/120 (75.8%; worst ear) and 79/120 (65.8%; better ear). Using Chang grading, hearing loss was diagnosed in 85/119 (71.4%; worst ear) versus 75/119 (63.0%; better ear). No TPMT or COMT single-nucleotide polymorphisms (SNPs) were associated with ototoxicity. ACYP2 SNP rs1872328 was associated with ototoxicity (P=0.027; worst ear). Meta-analysis of our data with that reported in previous studies showed the pooled odds ratio (OR) to be statistically significant for both the COMT SNP rs4646316 (OR: 1.50; 95% confidence interval: 1.15-1.95) and the ACYP2 SNP rs1872328 (OR: 5.91; 95% confidence interval: 1.51-23.16).
conclusionWe showed an association between the ACYP2 polymorphism and cisplatin-induced ototoxicity, but not with the TPMT and COMT. A meta-analysis was statistically significant for both the COMT rs4646316 and the ACYP2 rs1872328 SNPs. Grading the hearing of children with asymmetric hearing loss requires additional clarification.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.