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

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.

• Authors: Chalirmporn Atasilp, Mohitosh Biswas, Pimonpan Jinda, Nutthan Nuntharadthanaphong, Jiratha Rachanakul, Yaowaluck Hongkaew, Natchaya Vanwong, Surasak Saokaew, Chonlaphat Sukasem
• Journal: Clinical and translational science (Clin Transl Sci) Vol. 15 Issue 7 Pg. 1613-1633 (07 2022) ISSN: 1752-8062 [Electronic] United States
• PMID: 35506159 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Chemical References

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

Topics

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