Cancer Chemotherapy and Pharmacology

, Volume 82, Issue 1, pp 149–157 | Cite as

Possible association of CAG repeat polymorphism in KCNN3 encoding the potassium channel SK3 with oxaliplatin-induced neurotoxicity

  • Benjamin Anon
  • Bérenger Largeau
  • Alban Girault
  • Aurélie Chantome
  • Morgane Caulet
  • Clémence Perray
  • Driffa Moussata
  • Christophe Vandier
  • Chantal Barin-Le Guellec
  • Thierry Lecomte
Original Article



Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN.

Materials and methods

We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density. A retrospective study was carried out on patients with colorectal cancer who had received oxaliplatin-based chemotherapy. DNA for KCNN3 genotyping was extracted from leukocytes. The region containing the CAG repeats was amplified by PCR and the products separated by capillary electrophoresis for length analysis. The patients were divided into three groups depending on whether they carried two short alleles, one short allele and one long allele, or two long alleles. The primary endpoint was the onset of grade 2 or 3 neuropathy to oxaliplatin.


There was no difference in current density, but oxaliplatin induced a differential effect on apamin-sensitive current density between the two isoforms expressed in the HEK cell lines. There was a significant reduction of store-operated calcium entry into cells expressing the short and more active isoform only after high concentration of oxaliplatin exposition. Eighty-six patients were included in the clinical study. There was no significant association between OIN and KCNN3 polymorphism for the three groups.


We observed a slight association between OIN and CAG repeat polymorphisms of the KCNN3 gene in a preclinical model, but not a clinical study.


Neuropathy Platinum KCNN3 SK3 channel Oxaliplatin 



The authors would like to thank Network “Ion channels and cancer—Canceropôle Grand Ouest”, (IC-CGO) France ( Prof. Dr. Luis A. Pardo (Max-Planck-Institute of Experimental Medicine, Germany) kindly gave us HEK cells expressing long and short SK3.


A. Girault had a fellowship from the “Fondation de France”.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Benjamin Anon
    • 1
  • Bérenger Largeau
    • 2
  • Alban Girault
    • 3
  • Aurélie Chantome
    • 4
  • Morgane Caulet
    • 1
  • Clémence Perray
    • 1
  • Driffa Moussata
    • 1
  • Christophe Vandier
    • 4
  • Chantal Barin-Le Guellec
    • 2
    • 5
  • Thierry Lecomte
    • 1
    • 3
  1. 1.Department of Gastroenterology and Digestive Oncology, Service d’Hépato-gastro-entérologieHôpital Trousseau, CHRU de ToursToursFrance
  2. 2.Department of Molecular BiologyHôpital Bretonneau, CHRU de ToursToursFrance
  3. 3.UMR CNRS 7292 (GICC), Université François RabelaisToursFrance
  4. 4.INSERM, UMR 1069, Université François RabelaisToursFrance
  5. 5.INSERM, UMR 850, Université de LimogesLimogesFrance

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