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

Effects of UGT1A1*6 and UGT1A1*28 genetic polymorphisms on irinotecan-induced severe toxicities in Asian cancer patients are inconclusive. Also, ABCC2 c.3972CT 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.3972CT genetic variants. A PubMed literature search for eligible studies was conducted. Odds ratios (ORs) were measured using RevMan software where p values0.05 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.3972CT 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.