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. 2016 Aug 22;7(38):61970–61987. doi: 10.18632/oncotarget.11486

Table 7. Toxic events significantly associated with genotypes in relation to methotrexate or doxorubicin, cisplatin and ifosfamide by logistic regression analyses.

Drug (cycles) Toxic events Polymorphism Univariate logistic regression Multivariate logistic regression
OR (95% CI) p Adjusted OR (95% CI) p
Methotrexate (n = 520) Nausea/Vomiting ABCC2_3972A/G [WT] 3.15 (1.06–9.37) 0.039
Hepatotoxicity (Transaminases grade 4) ABCB1_1236T/C [HET + VAR]
ABCC2_1249A/G [WT]
GGH_16T/C [WT]
2.21 (1.22–4.00)
2.48 (1.47–4.18)
2.93 (1.53–5.62)
0.009
0.001
0.001
2.46 (1.29–4.72)
2.28 (1.31–3.96)
3.05 (1.57–5. 92)
0.001
0.004
0.001
Doxorubicin/ Cisplatin/ Ifosfamide (n = 488) Leukopenia grade 4 ABCC2_1249A/G [HET + VAR]
MTHFR_1298A/C [HET + VAR]
2.80 (1.63–4.83)
2.19 (1.26–3.82)
< 0.001
0.006
2.19 (1.23–3.92)
1.75 (0.97–3.13)
0.008
0.063
Thrombocytopenia grade 4
Red blood cells transfusion
Platelet transfusion
Nausea/Vomiting
ABCC2_1249A/G [HET + VAR]
ABCC2_1249A/G [HET + VAR]
ABCC2_1249A/G [HET + VAR]
ABCC2_3972A/G [WT]
4.35 (2.17–8.77)
2.13 (1.12–4.07)
3.55 (1.59–7.87)
2.28 (1.02–5.07)
< 0.0001
0.022
0.002
0.045

OR, Odd ratio; CI: confidence interval; p values refer to the genotype with higher risk which is given in brackets; WT, wild-type; HET + VAR, heterozygous + variant.