CYP2J2 ∗ 7 Genotype Predicts Risk of Chemotherapy-Induced Hematologic Toxicity and Reduced Relative Dose Intensity in Ethiopian Breast Cancer Patients.

Chemotherapy-induced hematologic toxicity is the primary reasons of dose reductions and/or delays, low relative dose intensity (RDI), and predicts anticancer response. We investigated the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced RDI in Ethiopian breast cancer patients, and implication of pharmacogenetics variations. Breast cancer patients (n = 249) were enrolled prospectively to receive cyclophosphamide based chemotherapy. Hematological toxicity (neutropenia, anemia, and thrombocytopenia) were monitored throughout chemotherapy cycle. The primary and secondary outcomes were incidence of grade 3 or 4 toxicity and reduced RDI, respectively. CYP2B6*6, CYP3A5*3, CYP2C9 (*2,*3), CYP2C19 (*2,*3), CYP2J2*7, POR*28, and ABCB1 (rs3842) genotyping were done. Cox proportional hazard and logistic regression were used to estimate risk predictors of toxicity and reduced RDI, respectively. Majority (73.5%) of the patients were < 45 years of age. The incidence of grade 3 or 4 hematological toxicity was 51.0% (95% CI = 44.54-57.46%). Multivariate Cox proportional hazard regression indicated CYP2J2*7 genotype [Hazard ratio (HR) = 1.82; 95% CI = 1.14-2.90], pretreatment grade 1 leukopenia (HR = 2.75; 95% CI = 1.47-5.15) or grade 1 or 2 neutropenia (HR = 2.75; 95% CI = 1.73-4.35) as significant predictors of hematologic toxicities. The odds of having hematologic toxicities was lower in CYP2C9*2 or*3 carriers (p = 0.024). The prevalence of reduced RDI was 56.6% (95% CI = 50.3-62.9%). Higher risk of reduced RDI was associated with CYP2J2*7 allele [Adjusted odds ratio (AOR) = 2.79; 95% CI = 1.21-6.46], BMI*18.4 kg/m(2) (AOR = 5.98; 95% CI = 1.36-26.23), baseline grade 1 leukopenia (AOR = 6.09; 95% CI = 1.24-29.98), and baseline neutropenia (AOR = 3.37; 95% CI = 1.41-8.05). The odds of receiving reduced RDI was lower in patients with CYP2B6 *6/*6 genotype (AOR = 0.19; 95% CI = 0.06-0.77). We report high incidence of chemotherapy-induced hematological toxicities causing larger proportion of patients to receive reduced RDI in Ethiopian breast cancer patients. Patients carrying CYP2J2*7 allele and low baseline blood counts are at a higher risk for chemotherapy-induced hematologic toxicities and receiving reduced RDI, and may require prior support and close follow up during chemotherapy.