3.2.2 Association of UGT1A1*28 with irinotecan induced severe toxicity
A total of 27 studies assessed the risk of neutropenia in cancer patients taking irinotecan and carried UGT1A1*28 genetic polymorphism. It was found that the aggregated risk of neutropenia was significantly higher in patients inherited heterozygous and homozygous variant of the UGT1A1*28 (UGT1A1*1/*28 andUGT1A1*28/*28 ) compared to the patients carried wild type genotype i.e. UGT1A1*1/*1 (OR 1.86; 95% CI 1.52–2.27;P < 0.00001), that was mainly driven from the patients who carried homozygous variant i.e. UGT1A1*28/*28 (OR 3.11; 95% CI 1.71–5.63; P =0.0002) than heterozygous variant i.e. UGT1A1*1/*28 (OR 1.53; 95% CI 1.18–2.00; P =0.001), as shown in Figure 3A.
When estimated pooled risk for diarrhea from 20 studies, it was found that the patients inherited heterozygous and homozygous variant of theUGT1A1*28 (UGT1A1*1/*28 and UGT1A1*28/*28 ) were significantly associated with increased risk of diarrhea (OR 2.74; 95% CI 2.14–3.50; P <0.00001) compared to the patients with wild type genotype (UGT1A1*1/*1), as shown in Figure 3B. Further analysis indicated that the risk of diarrhea was much striking in patients carried homozygous variant i.e. UGT1A1*28/*28 (OR 5.70; 95% CI 3.10–10.50; P <0.00001) compared to the patients with heterozygous variant i.e. UGT1A1*1/*28 (OR 2.18; 95% CI 1.58–3.02; P <0.00001), Figure 3B.