BACKGROUND: Whether UGT1A1*28 genotype is associated with clinical outcomes of 
irinotecan (IRI)-based chemotherapy in Colorectal cancer (CRC) is an important 
gap in existing knowledge to inform clinical utility. Published data on the 
association between UGT1A1*28 gene polymorphisms and clinical outcomes of 
IRI-based chemotherapy in CRC were inconsistent.
METHODOLOGY/PRINCIPAL FINDINGS: Literature retrieval, trials selection and 
assessment, data collection, and statistical analysis were performed according 
to the PRISMA guidelines. Primary outcomes included therapeutic response (TR), 
progression-free survival (PFS) and overall survival (OS). We calculated odds 
ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI). Twelve 
clinical trials were included. No statistical heterogeneity was detected in 
analyses of all studies and for each subgroup. Differences in TR, PFS and OS for 
any genotype comparison, UGT1A1*28/*28 versus (vs) UGT1A1*1/*1 (homozygous 
model), UGT1A1*1/*28 vs UGT1A1*1/*1 (heterozygous model), and UGT1A1*28/*28 vs 
all others (recessive model, only for TR) were not statistically significant. 
IRI dose also did not impact upon TR and PFS differences between UGT1A1 genotype 
groups. A statistically significant increase in the hazard of death was found in 
Low IRI subgroup of the homozygous model (HR = 1.48, 95% CI = 1.06-2.07; P = 
0.02). The UGT1A1*28 allele was associated with a trend of increase in the 
hazard of death in two models (homozygous model: HR = 1.22, 95% CI = 0.99-1.51; 
heterozygous model: HR = 1.13, 95% CI = 0.96-1.32). These latter findings were 
driven primarily by one single large study (Shulman et al. 2011).
CONCLUSIONS/SIGNIFICANCE: UGT1A1*28 polymorphism cannot be considered as a 
reliable predictor of TR and PFS in CRC patients treated with IRI-based 
chemotherapy. The OS relationship with UGT1A1*28 in the patients with lower-dose 
IRI chemotherapy requires further validation.