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

Abstract: Background: 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. It was aimed 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. Methods: Literature was searched in PubMed for eligible studies. Odds ratios (ORs) were measured using RevMan software where P-values<0.05 were statistically significant. Results: Patients 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 carried 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 with heterozygous variants. However, patients carried ABCC2 c.3972C>T genetic variant were not significantly associated with neutropenia (OR 1.67; 95% CI 0.98–2.84; P=0.06) but reduced diarrhea significantly (OR 0.31; 95% CI 0.11–0.81; P=0.02). Conclusions: Both UGT1A1*6 and UGT1A1*28 genetic variants should screen in Asian cancer patients to reduce substantially irinotecan-induced severe toxicities.