Integrin beta-3 L33P: a new insight into the pathogenesis of chronic oxaliplatin-induced peripheral neuropathy?

Eur J Neurol. 2010 Jul;17(7):963-8. doi: 10.1111/j.1468-1331.2010.02966.x. Epub 2010 Feb 23.

Abstract

Aim: To assess the significance of the ITGB3 polymorphism at residue 33 (ITGB3 L33P) in the development of chronic oxaliplatin-induced peripheral neuropathy (OXLIPN).

Methods: Fifty-five patients with advanced colorectal cancer were genotyped, using allele-specific primers and sybr green in real-time PCR. Patients had received adjuvant oxaliplatin-based chemotherapy. The severity of the OXLIPN was defined by means of the clinical total neuropathy score (TNSc). Following the discontinuation of treatment, 34/55 patients (61.8%) developed OXLIPN. Grade I neurotoxicity was revealed in 13 (38.2%) patients and grade II neurotoxicity in 21 (61.8%) patients.

Results: Patients without OXLIPN (n = 21) were 19% homozygous for C, 33.3% were heterozygous, and 47.7% were homozygous for T. The corresponding percentages for patients developing any grade of OXLIPN (n = 34) were similar. About half of patients (46.1%) with grade I OXLIPN were heterozygotes (CT), 23.1% were CC, and 30.8% were TT. The majority of patients with grade II OXLIPN were TT (66.7%) with the remaining 33.3% being CT. The TT genotype was associated with increased severity of OXLIPN compared to the genotypes containing the C allele (P = 0.044).

Conclusion: The ITGB3 L33P seems to be unrelated to the development of OXLIPN, but it appears to be related to its severity.

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects*
  • Chronic Disease
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Female
  • Humans
  • Iatrogenic Disease / prevention & control
  • Integrin beta3 / physiology*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / adverse effects*
  • Oxaliplatin
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / diagnosis*
  • Peripheral Nervous System Diseases / metabolism
  • Pilot Projects
  • Severity of Illness Index

Substances

  • Antineoplastic Agents
  • Integrin beta3
  • Organoplatinum Compounds
  • Oxaliplatin