Genetic polymorphisms of SCN9A are associated with oxaliplatin-induced neuropathy

BMC Cancer

Research Article

Cristina Rodríguez-Antona¹  Lara Sánchez-Barroso²  María Apellániz-Ruiz²  Nuria Rodriguez-Salas³  César Gómez-Raposo⁴  Miriam López-Gómez⁴  María Sereno⁴  María Merino⁴  Juan Moreno Rubio⁴  Sandra Falagan⁴  Enrique Casado⁴  Francisco Zambrana Tébar⁴  Gerardo Gutiérrez-Gutiérrez⁵ 

[1] Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Center (CNIO), Madrid, Spain;ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain;Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain;Medical Oncologist, Medical Oncology Department, La Paz University Hospital, Madrid, Spain;Medical Oncology Department, Infanta Sofía University Hospital, SS de los Reyes, Madrid, Spain;Neurology Department, Infanta Sofía University Hospital, SS de los Reyes, Madrid, Spain;

关键词: Oxaliplatin neuropathy;    Calcium channel;    SCN9A;   

DOI  :  10.1186/s12885-016-3031-5

 received in 2016-08-20, accepted in 2016-12-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundOxaliplatin 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.MethodsBlood 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.ResultsWe 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.ConclusionSCN9A rs6746030 was associated with protection for severe oxaliplatin-induced peripheral neuropathy. The validation of this exploratory study is ongoing in an independent series.

【 授权许可】

CC BY   
© The Author(s). 2017