Table 5

Summary of genotype-phenotype associations

PolymorphismPhenotypic consequenceaPb
ABCB1 1236C>TIrinotecan total AUC increased0.038 (46)
SN-38 total AUC increased0.031 (46)
SN-38 lactone CL reduced0.015 (46)
ABCB1 3435C>TIrinotecan lactone AUC0.100 (59)
ABCB1 2677G>T/AIrinotecan lactone CL0.083 (53)
ABCC1 14008G>ASN-38 lactone CL0.127 (64)
ABCC1 34215C>GAPC AUC0.345 (60)
CYP3A4*1B SN-38 lactone CL0.213 (65)
CYP3A4*3 Irinotecan lactone CL0.059 (64)
CYP3A5*3C Irinotecan carboxylate CL0.174 (64)
UGT1A1*28 SN-38G/SN-38 AUC ratio0.221 (53)
  • a Represents the best association (lowest P) between a given polymorphism (wild-type versus heterozygous variant versus homozygous variant type patients) and a change in a pharmacokinetic parameter, with number of patients in parenthesis.

  • b Kruskal-Wallis test following logarithmic transformation for data with a skewed distribution; except for ABCB1 1236 C>T, no statistically significant associations were found.