Association Between ABCC2 Polymorphism and Hematological Toxicity in Patients with Esophageal Cancer Receiving Platinum Plus 5-Fluorouracil Therapy.

Platinum agents are taken up into cells by copper transporter (CTR) 1 (gene code: SLC31A1) and are excreted from cells by copper-transporting P-type adenosine triphosphatase (ATP7B) and multidrug resistance-associated protein (MRP) 2 (gene code: ABCC2). In addition, glutathione S transferase (GST) P1 is involved in the metabolism of platinum agents. The present study aimed to determine whether the rate of grade 3–4 hematological toxicity associated with platinum plus 5-fluorouracil (5-FU) therapy in 239 patients with esophageal cancer was affected by the SLC31A1 rs10981694A>C and rs12686377G>T, ATP7B rs9535828A>G, GSTP1 rs1695A>G, and ABCC2 −24C>T polymorphisms. Chemotherapy consisted of protracted infusion of 5-FU (800 mg/m2/day) on days 1–5 and cisplatin or nedaplatin (80 mg/m2/day) on day 1. A total of 82 of 239 patients developed grade 3–4 hematological toxicity after chemotherapy. Univariate analysis showed that ABCC2 −24C/T + T/T genotypes (P = 0.038), radiation therapy (P = 0.013), baseline white blood cell count < 6000/μL (P = 0.003), and baseline neutrophil count < 3900/μL (P = 0.021) were statistically significant predictors of grade 3–4 hematological toxicity. Multivariate analysis revealed that ABCC2 −24C/T + T/T genotypes (P = 0.036), radiation therapy (P = 0.005), and baseline white blood cell count < 6000/μL (P < 0.001) were significant risk factors. We determined that ABCC2 −24C>T is significantly associated with grade 3–4 hematological toxicity after platinum plus 5-FU therapy. These findings might contribute to improved treatment strategies for patients with esophageal cancer.