Association between ABCC2 polymorphism and hematological toxicity in patients with esophageal cancer receiving platinum plus 5-fluorouracil therapy
Association between ABCC2 polymorphism and hematological toxicity in patients with esophageal cancer receiving platinum plus 5-fluorouracil therapy
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DOI：
10.1007/s10388-021-00865-7
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发表时间：
2021-08-04
期刊：
影响因子：
2.4
通讯作者：
Miura, Masatomo
中科院分区：
文献类型：
--
作者：
Fujita, Kazuma;Motoyama, Satoru;Miura, Masatomo
背景铂类药物通过铜转运蛋白（CTR）1（基因编码：SLC 31 A1）进入细胞，并通过铜转运蛋白P-型三磷酸腺苷酶（ATP 7 B）和多药耐药相关蛋白（MRP）2（基因编码：ABCC 2）排出细胞。此外，谷胱甘肽S转移酶（GST）P1参与铂类药物的代谢。本研究旨在确定239例食管癌患者接受铂类联合5-氟尿嘧啶（5-FU）治疗后3-4级血液学毒性的发生率是否受SLC 31 A1 rs 10981694 A>C和rs 12686377 G>T、ATP 7 B rs 9535828 A>G、GST P1 rs 1695 A>G和ABCC 2 - 24 C>T多态性的影响。方法化疗方案为5-FU（800 mg/m2/d），第1-5天，顺铂或奈达铂（80 mg/m2/d），第1天。结果239例患者化疗后发生3-4级血液学毒性反应82例。单因素分析显示，ABCC 2 - 24 C/T + T/T基因型（P = 0.038）、放射治疗（P = 0.013）、基线白色细胞计数< 6000/mu L（P = 0.003）和基线中性粒细胞计数< 3900/mu L（P = 0.021）是3-4级血液学毒性的统计学显著预测因素。多因素分析显示ABCC 2 - 24 C/T + T/T基因型（P = 0.036）、放疗（P = 0.005）和基线白色细胞计数< 6000/mu L（P < 0.001）是显著的危险因素。结论我们确定ABCC 2 - 24 C>T与铂类联合5-FU治疗后3-4级血液学毒性显著相关。这些发现可能有助于改善食道癌患者的治疗策略。
Background 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. Methods Chemotherapy consisted of protracted infusion of 5-FU (800 mg/m(2)/day) on days 1-5 and cisplatin or nedaplatin (80 mg/m(2)/day) on day 1. Results 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/mu L (P = 0.003), and baseline neutrophil count < 3900/mu L (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/mu L (P < 0.001) were significant risk factors. Conclusions 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.