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Association between genetic polymorphisms and platinum-induced ototoxicity in children.

ABSTRACT: Platinum is extensively used in the treatment of several childhood cancers. However, ototoxicity is one of the most notable adverse effects, especially in children. Several studies suggest that genetics may predict its occurrence. Here, polymorphisms associated with platinum-induced ototoxicity were selected from the literature and were investigated in a pediatric population treated with platinum-based agents. In this retrospective study, patients treated with cisplatin and/or carboplatin were screened. The patients with pre- and post-treatment audiogram (Brock criteria) available were included. We selected polymorphisms that have previously been associated with cisplatin ototoxicity with a minor allele frequency ?30%. Deletion of GSTM1 and GSTT1, rs1799735 (GSTM3), rs1695 (GSTP1), rs4880 (SOD2), rs2228001 (XPC), rs1799793 (XPD) and rs4788863 (SLC16A5) were investigated. Data of one hundred and six children matching the eligible criteria were analyzed. Thirty-three patients (31%) developed ototoxicity (with a Brock grade ?2). The probability of hearing loss increased significantly in patients carrying the null genotype for GSTT1 (P = 0.03), A/A genotype at rs1695 (P = 0.01), and C/C genotype at rs1799793 (P = 0.008). We also showed an association of the cumulative doses of carboplatin with cisplatin ototoxicity (P <0.05). To conclude, deletion of GSTT1, rs1695 and rs1799793 may constitute potential predictors of platinum-induced ototoxicity.

SUBMITTER: Lui G

PROVIDER: S-EPMC6089394 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Association between genetic polymorphisms and platinum-induced ototoxicity in children.

Lui Gabrielle G Bouazza Naïm N Denoyelle Françoise F Moine Marion M Brugières Laurence L Chastagner Pascal P Corradini Nadège N Entz-Werle Natacha N Vérité Cécile C Landmanparker Judith J Sudour-Bonnange Hélène H Pasquet Marlène M Verschuur Arnauld A Faure-Conter Cécile C Doz François F Tréluyer Jean-Marc JM

Oncotarget 20180720 56

Platinum is extensively used in the treatment of several childhood cancers. However, ototoxicity is one of the most notable adverse effects, especially in children. Several studies suggest that genetics may predict its occurrence. Here, polymorphisms associated with platinum-induced ototoxicity were selected from the literature and were investigated in a pediatric population treated with platinum-based agents. In this retrospective study, patients treated with cisplatin and/or carboplatin were s ...[more]

PMID: 30112115

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Project description:Aim:Dental enamel, the most rigid biological tissue of the tooth known to mankind, is the most integral and fundamental part of the tooth. Enamel matrixes compile 5% of Enamelin peptides and at the time of tooth development, they are considered to effect the formation and elongation of enamel crystallites. ENAM plays critical role in enamel formation. Any changes in ENAM may affect the thickness of enamel and may lead to dental caries. The present study is aimed to evaluate the association of ENAM gene polymorphisms and susceptibility of dental caries development risk. Material and methods:The present study was carried out on 168 South Indian children, children's with dental caries were included in study. Written consent was taken from their parents/guardians. Additionally 193 healthy individuals were enrolled as controls. Sampling was done after dental examination of the individuals. Three ENAM gene single nucleotide polymorphisms (SNPs) were rs7671281, rs3796704 and rs12640848 was genotyped to check their role in susceptibility of dental caries development risk. Results:Out of three SNPs rs7671281 showed statistically significant risk association with dental caries susceptibility in this ethnic population at heterozygous allele CT (OR: 1.939, p?=?.01865) and with minor allele T (OR: 1.451, p?=?.001292). SNP rs3796704 showed significant protective association with dental caries in Indian population at heterozygous allele GA (OR: 0.409, p?=?.0192) and with minor allele A (OR: 0.645, p?=?.00875). SNP rs12640848 showed significant protective association with dental caries in Indian population at heterozygous allele AG (OR: 3.041, p?=?.00642) and with minor allele G (OR: 1.478, p?=?.02184). Preliminary insilico analysis also showed that rs7671281 (Ile648Thr) amino acid change will cause the structural and functional changes in ENAM protein. Conclusions:In the present study significant association was observed between ENAM gene SNP rs7671281 and dental caries susceptibility in South Indian children. These results suggested that ENAM gene variants may contribute to dental caries in children.

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Association between genetic polymorphisms and platinum-induced ototoxicity in children.

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Association between genetic polymorphisms and platinum-induced ototoxicity in children.

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