Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C>T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis

Clin Transl Sci. 2022 Jul;15(7):1613-1633. doi: 10.1111/cts.13277. Epub 2022 May 31.

Abstract

Effects of UGT1A1*6 and UGT1A1*28 genetic polymorphisms on irinotecan-induced severe toxicities in Asian cancer patients are inconclusive. Also, ABCC2 c.3972C>T may affect toxicity of irinotecan. The aim was to assess the aggregated risk of neutropenia or diarrhea in Asian cancer patients taking irinotecan and inherited UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C>T genetic variants. A PubMed literature search for eligible studies was conducted. Odds ratios (ORs) were measured using RevMan software where p values <0.05 were statistically significant. Patients that inherited both UGT1A1*6 and UGT1A1*28 genetic variants (heterozygous: UGT1A1*1/*6 + *1/*28 and homozygous: UGT1A1*6/*6 + *28/*28) were significantly associated with increased risk of neutropenia and diarrhea compared to patients with UGT1A1*1/*1 (neutropenia: OR 2.89; 95% CI 1.97-4.23; p < 0.00001; diarrhea: OR 2.26; 95% CI 1.71-2.99; p < 0.00001). Patients carrying homozygous variants had much stronger effects in developing toxicities (neutropenia: OR 6.23; 95% CI 3.11-12.47; p < 0.00001; diarrhea: OR 3.21; 95% CI 2.13-4.85; p < 0.00001) than those with heterozygous variants. However, patients carrying the ABCC2 c.3972C>T genetic variant were not significantly associated with neutropenia (OR 1.67; 95% CI 0.98-2.84; p = 0.06) and were significantly associated with a reduction in irinotecan-induced diarrhea (OR 0.31; 95% CI 0.11-0.81; p = 0.02). Asian cancer patients should undergo screening for both UGT1A1*6 and UGT1A1*28 genetic variants to reduce substantially irinotecan-induced severe toxicities.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic* / adverse effects
  • Antineoplastic Agents, Phytogenic* / therapeutic use
  • Diarrhea* / chemically induced
  • Diarrhea* / genetics
  • Genotype
  • Glucuronosyltransferase* / genetics
  • Humans
  • Irinotecan* / adverse effects
  • Irinotecan* / therapeutic use
  • Neoplasms* / drug therapy
  • Neutropenia* / chemically induced
  • Neutropenia* / genetics
  • Polymorphism, Genetic
  • Topoisomerase I Inhibitors* / adverse effects
  • Topoisomerase I Inhibitors* / therapeutic use

Substances

  • Antineoplastic Agents, Phytogenic
  • Topoisomerase I Inhibitors
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase