On evaluating higher order gene-gene interaction models by MDR analysis, CYP3A5*3; ABCB11236C>T and ABCB1 2677G>T/A; ABCB1 3435C>T and CYP1B1*3 showed significant association with treatment response, grade 2-4 anemia and dose delay/reduction due to neutropenia (P=0.024, P=0.004, P=0.026), respectively.
The multivariate logistic regression analysis revealed that the ABCB1 2677G>T/A polymorphism was a strong predictor of grade 3 or greater neutropenia (odds ratio: 3.76; 95% confidence interval: 1.44-9.81; p = 0.007).
Meta-analysis showed an decreased risk of irinotecan-induced neutropenia in patients expressing ABCB1 2677G>T/G (odds ratio [OR]: 0.24; 95% CI: 0.1-0.59; p = 0.002) but increased risk for ABCC2 3972T>T (OR: 1.67; 95% CI: 1.01-2.74; p = 0.04).