Liability of the voltage-gated potassium channel KCNN3 repeat polymorphism to acute oxaliplatin-induced peripheral neurotoxicity

J Peripher Nerv Syst. 2019 Dec;24(4):298-303. doi: 10.1111/jns.12347. Epub 2019 Oct 16.


Thus far, there are conflicting results on the causal role of K+ channels in the pathogenesis of acute oxaliplatin-induced peripheral neurotoxicity (OXAIPN). As such, we tested the hypothesis that the voltage-gated K+ channel KCNN3 repeat polymorphism confers liability to acute OXAIPN. DNA from 151 oxaliplatin-treated patients for colorectal cancer was extracted and genotyped. The incidence of acute OXIPN was measured by the OXA-neuropathy questionnaire, while the severity of acute OXAIPN was scored basing on the number of symptoms reported by the patients at each clinical assessment. The increased number of acute symptoms was considered as being suggestive of an increased severity of acute OXAIPN. A total of 130/151 (86.1%) patients developed any grade of acute OXAIPN. Grade I acute neurotoxicity was revealed in 43 (28.5%) patients; grade II in 34 (22.5%); and grade III in 53 (53.1%) patients. Genotyping revealed alleles carrying 11 to 20 CAG repeats. The majority of patients were heterozygous (131; 89.4%). The most common numbers of CAG repeats were 15 (n = 46), 16 (n = 53), and 17 (n = 95). Patients carrying alleles with either 15 to 17 CAG repeats (P = .601) did not experience a higher incidence of grade III (treatment-emergent) acute OXAIPN. Likewise, no increased incidence of acute treatment-emergent OXAIPN was noted in heterozygous patients carrying either two short alleles (<19 CAG repeats) or one short and one long (≥19 CAG repeats) allele (P = .701). Our results do not support a causal relationship between the KCNN3CAG repeat polymorphism and acute OXΑIPN.

Keywords: KCNN3; biomarker; neurotoxicity; oxaliplatin; pathogenesis; potassium channels.

MeSH terms

  • Aged
  • Antineoplastic Agents / toxicity*
  • Colorectal Neoplasms / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurotoxicity Syndromes* / etiology
  • Neurotoxicity Syndromes* / genetics
  • Neurotoxicity Syndromes* / physiopathology
  • Oxaliplatin / toxicity*
  • Peripheral Nervous System Diseases* / chemically induced
  • Peripheral Nervous System Diseases* / genetics
  • Peripheral Nervous System Diseases* / physiopathology
  • Polymorphism, Genetic
  • Severity of Illness Index
  • Trinucleotide Repeats


  • Antineoplastic Agents
  • Oxaliplatin