3.2 Outcomes of meta-analysis
3.2.1 Association ofUGT1A1*6 with irinotecan induced severe toxicity
The association of UGT1A1*6 genetic polymorphism with irinotecan induced
neutropenia and diarrhea were assessed from 23 and 18 studies,
respectively. After pooled estimation it was found that the aggregated
risk of neutropenia was significantly higher in cancer patients
inherited heterozygous and homozygous variant of the UGT1A1*6(UGT1A1*1/*6 and UGT1A1*6/*6 ) compared to the patients
carried wild type genotype i.e. UGT1A1*1/*1 (OR 2.00; 95% CI
1.64–2.44; P <0.00001), as shown in Figure 2A. However,
the risk of neutropenia was much stronger in patients carried homozygous
variant i.e. UGT1A1*6/*6 (OR 3.94; 95% CI 2.51–6.20;P <0.00001) compared to the patients carried
heterozygous variant i.e. UGT1A1*1/*6 (OR 1.70; 95% CI
1.33–2.18; P <0.0001), Figure 2A
It was also found that the patients harbored heterozygous and homozygous
variant of the UGT1A1*6 (UGT1A1*1/*6 andUGT1A1*6/*6 ) were significantly associated with increased risk of
diarrhea compared to the patients inherited wild type genotype i.e.UGT1A1*1/*1 (OR 2.52; 95% CI 1.65–3.82;P <0.0001), as driven from the patients with homozygous
variant i.e. UGT1A1*6/*6 (OR 4.65; 95% CI 1.88–11.53;P =0.009), but not the patients with heterozygous variant i.e.UGT1A1*1/*6 (OR 1.77; 95% CI 0.94–3.33; P =0.08) as shown
in Figure 2B.