Genetic polymorphisms of SCN9A are associated with oxaliplatin-induced neuropathy
EntityUAM. Departamento de Medicina
10.1186/s12885-016-3031-5BMC Cancer 17 (2017): 63
Funded byThis work was supported by projects from the “Spanish Ministry of Economy and Competiveness” (grant number SAF2015-64850-R) and from Carlos III Health Institute project: PI12/02824
ProjectGobierno de España. SAF2015-64850-R; Gobierno de España. PI12/02824
SubjectsOxaliplatin neuropathy; Calcium channel; SCN9A; Medicina
Rights© 2017 The Author(s)
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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
Google Scholar:Sereno, María - Gutiérrez-Gutiérrez, Gerardo - Moreno Rubio, Juan - Apellániz-Ruiz, María - Sánchez-Barroso, Lara - Casado, Enrique - Falagan, Sandra - López-Gómez, Miriam - Merino, María - Gómez-Raposo, César - Rodríguez Salas, Nuria - Zambrana Tébar, Francisco - Rodríguez-Antona, Cristina
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