Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study

Autor: Clemens, Eva, Broer, Linda, Langer, Thorsten, Uitterlinden, André G., de Vries, Andrica C. H., van Grotel, Martine, Pluijm, Saskia F. M., Binder, Harald, Byrne, Julianne, Broeder, Eline van Dulmen-den, Crocco, Marco, Kaiser, Melanie, Kenborg, Line, Winther, Jeanette F., Rechnitzer, Catherine, Hasle, Henrik, van der Kooi, Anne-Lotte F., Kremer, Leontien C., van der Pal, Heleen, Parfitt, Ross, Deuster, Dirk, Matulat, Peter, Spix, Claudia, Tillmanns, Amelie, Tissing, Wim J. E., Maier, Lara, am Zehnhoff-Dinnesen, Antoinette, Zolk, Oliver, Kaatsch, P., Grabow, D., Campbell, H., O’Brien, K., Kremer, L.C.M., van Dulmen-den Broeder, E., van den Berg, M.H., van den Heuvel-Eibrink, M.M., Borgmann-Staudt, A., Kuehni, C.E., Haupt, R., Kepak, T., Berger, C., Winther, J.F., Kruseova, J., Calaminus, G., Baust, K., Dirksen, U., Kuehni, Claudia E., van den Heuvel-Eibrink, Marry M.
Přispěvatelé: Guided Treatment in Optimal Selected Cancer Patients (GUTS), Pediatric surgery, CCA - Cancer biology and immunology, Amsterdam Reproduction & Development (AR&D), Internal Medicine, Pediatrics, Obstetrics & Gynecology
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Pharmacogenomics journal, 20(2), 294-305. Nature Publishing Group
Clemens, E, Broer, L, Langer, T, Uitterlinden, A G, de Vries, A C H, van Grotel, M, Pluijm, S F M, Binder, H, Byrne, J, Broeder, E V D, Crocco, M, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Winther, J F, Rechnitzer, C, Hasle, H, Kepak, T, van der Kooi, A-L F, Kremer, L C, Kruseova, J, Kuehni, C E, van der Pal, H, Parfitt, R, Deuster, D, Matulat, P, Spix, C, Tillmanns, A, Tissing, W J E, Maier, L, Am Zehnhoff-Dinnesen, A, Zolk, O, van den Heuvel-Eibrink, M M & PanCareLIFE Consortium 2020, ' Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach : The International PanCareLIFE Study ', The Pharmacogenomics Journal, vol. 20, no. 2, pp. 294-305 . https://doi.org/10.1038/s41397-019-0113-1
Clemens, E, Broer, L, Langer, T, Uitterlinden, A G, de Vries, A C H, van Grotel, M, Pluijm, S F M, Binder, H, Broeder, E V D, Crocco, M, Kenborg, L, Winther, J F, Rechnitzer, C, Hasle, H, van der Kooi, A-L F, Kremer, L C, van der Pal, H, Parfitt, R, Deuster, D, Matulat, P, Spix, C, Tillmanns, A, Tissing, W J E, Maier, L, am Zehnhoff-Dinnesen, A, Zolk, O, van den Heuvel-Eibrink, M M, Kaatsch, P, on behalf of the PanCareLIFE consortium & van den Heuvel-Eibrink, M M 2020, ' Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study ', Pharmacogenomics Journal, vol. 20, no. 2, pp. 294-305 . https://doi.org/10.1038/s41397-019-0113-1
Pharmacogenomics Journal, 20(2), 294-305. Nature Publishing Group
ISSN: 1470-269X
Popis: Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8–21.5; P = 5.6 × 10−7) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2: OR: 2.4; 95% CI: 1.3–4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04–14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07–2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.
Databáze: OpenAIRE
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