Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: A genome-wide study replication and meta-analysis

Salvatore Terrazzino, Andreas A. Argyriou, Sarah Cargnin, Anna G. Antonacopoulou, Chiara Briani, Jordi Bruna, Roser Velasco, Paola Alberti, Marta Campagnolo, Sara Lonardi, Diego Cortinovis, Marina Cazzaniga, Cristina Santos, Haralabos P. Kalofonos, Pier Luigi Canonico, Armando A. Genazzani, Guido Cavaletti

Research output: Contribution to journalArticle

Abstract

We aimed at validating the role of genetic variants identified by a recent genome-wide association study (GWAS) as determinants of chronic oxaliplatin-induced peripheral neurotoxicity (OXAIPN). Eight polymorphisms (rs10486003, rs2338, rs843748, rs797519, rs4936453, rs12023000, rs17140129, and rs6924717) were genotyped in a total of 150 colorectal cancer patients of Caucasian origin receiving oxaliplatin-based chemotherapy. The severity grade of chronic OXAIPN was assessed by NCI-CTC criteria and the clinical version of the Total Neuropathy Score© (TNSc©). None of the polymorphisms investigated was found associated with grade ≥ chronic OXAIPN (NCI-CTC criteria), while a nominal association emerged for ACYP2 rs843748 when using the TNSc© scale (dominant model: odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10-0.75, P=0.008). In the combined analysis of this results with data of the two previously published studies which assessed chronic OXAIPN by NCI-CTC criteria, evidence suggestive of association with chronic OXAIPN (NCI-CTC criteria) was found for ACYP2 rs843748 (dominant model: OR: 2.40, 95%CI: 1.40-5.24, P=0.027), which, however, did not remain significant after correction for multiple testing (threshold P-value

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalJournal of the Peripheral Nervous System
Volume20
Issue number1
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • chemotherapy-induced peripheral neuropathy
  • meta- analysis
  • neurotoxicity
  • oxaliplatin
  • polymorphisms

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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  • Cite this

    Terrazzino, S., Argyriou, A. A., Cargnin, S., Antonacopoulou, A. G., Briani, C., Bruna, J., Velasco, R., Alberti, P., Campagnolo, M., Lonardi, S., Cortinovis, D., Cazzaniga, M., Santos, C., Kalofonos, H. P., Canonico, P. L., Genazzani, A. A., & Cavaletti, G. (2015). Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: A genome-wide study replication and meta-analysis. Journal of the Peripheral Nervous System, 20(1), 15-23. https://doi.org/10.1111/jns.12110