Importance of UDP-glucuronosyltransferase 1A1*6 for irinotecan toxicities in Japanese cancer patients

Cancer Lett. 2008 Mar 18;261(2):165-71. doi: 10.1016/j.canlet.2007.11.009. Epub 2007 Dec 20.

Abstract

Recent pharmacogenetic studies on irinotecan have revealed the impact of UDP glucuronosyltransferase (UGT) 1A1*28 on severe irinotecan toxicities. Although the clinical role of UGT1A1*6, which is specifically detected in East Asian patients, in irinotecan toxicities is suggested, clear evidence remains limited. To examine the impact of *6, the association of UGT1A1 genotypes with severe irinotecan toxicities was retrospectively investigated in Japanese cancer patients. A significant *6-dependent increase in the incidence of grade 3 or 4 neutropenia was observed in 49 patients on irinotecan monotherapy (p=0.012). This study further clarifies the clinical importance of *6 in irinotecan therapy in East Asians.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Asian People / genetics
  • Bilirubin / blood
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Female
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Glucuronosyltransferase / metabolism
  • Humans
  • Incidence
  • Irinotecan
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Polymorphism, Genetic*
  • Retrospective Studies

Substances

  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Bilirubin
  • Camptothecin