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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Genetic polymorphisms of SCN9A are associated with oxaliplatin-induced neuropathy

Authors: María Sereno, Gerardo Gutiérrez-Gutiérrez, Juan Moreno Rubio, María Apellániz-Ruiz, Lara Sánchez-Barroso, Enrique Casado, Sandra Falagan, Miriam López-Gómez, María Merino, César Gómez-Raposo, Nuria Rodriguez-Salas, Francisco Zambrana Tébar, Cristina Rodríguez-Antona

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Oxaliplatin is a chemotherapy agent active against digestive tumors. Peripheral neuropathy is one of the most important dose-limiting toxicity of this drug. It occurs in around 60–80% of the patients, and 15% of them develop severe neuropathy. The pathophysiology of oxaliplatin neurotoxicity remains unclear. SCN9A is a gene codifying for a subtype sodium channel (type IX, subunit α) and mutations in this gene are involved in neuropathic perception. In this study we investigated whether SCN9A genetic variants were associated with risk of neurotoxicity in patients diagnosed of cancer on treatment with oxaliplatin.

Methods

Blood samples from 94 patients diagnosed of digestive cancer that had received oxaliplatin in adjuvant or metastatic setting were obtained from three hospitals in Madrid. These patients were classified into two groups: “cases” developed oxaliplatin-induced grade 3–4 neuropathy (n = 48), and “controls” (n = 46) had no neuropathy or grade 1. The neuropathy was evaluated by an expert neurologist and included a clinical examination and classification according to validated neurological scales: National Cancer Institute Common Toxicity Criteria (NCI-CTC), Oxaliplatin-Specific Neurotoxicity Scale (OSNS) and Total Neuropathy score (TNS). Genotyping was performed for 3 SCN9A missense polymorphisms: rs6746030 (R1150W), rs74401238 (R1110Q) and rs41268673 (P610T), and associations between genotypes and neuropathy were evaluated.

Results

We found that SCN9A rs6746030 was associated with protection for severe neuropathy (OR = 0.39, 95% CI = 0.16–0.96; p = 0.041). Multivariate analysis adjusting for diabetes provided similar results (p = 0.036). No significant differences in neuropathy risk were detected for rs74401238 and rs41268673.

Conclusion

SCN9A rs6746030 was associated with protection for severe oxaliplatin-induced peripheral neuropathy. The validation of this exploratory study is ongoing in an independent series.
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Metadata
Title
Genetic polymorphisms of SCN9A are associated with oxaliplatin-induced neuropathy
Authors
María Sereno
Gerardo Gutiérrez-Gutiérrez
Juan Moreno Rubio
María Apellániz-Ruiz
Lara Sánchez-Barroso
Enrique Casado
Sandra Falagan
Miriam López-Gómez
María Merino
César Gómez-Raposo
Nuria Rodriguez-Salas
Francisco Zambrana Tébar
Cristina Rodríguez-Antona
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-3031-5

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