Liang Yao, Maeda Osamu, Miyata Kazushi, Kanda Mitsuro, Sugita Shizuki, Shimizu Dai, Nishida Kazuki, Kodera Yasuhiro, Ando Yuichi
Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Chemother Pharmacol. 2024 Feb;93(2):121-127. doi: 10.1007/s00280-023-04607-7. Epub 2023 Oct 28.
This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer.
Preoperative DCF (docetaxel, 70 mg/m/day, day 1; cisplatin, 70 mg/m/day, day 1; fluorouracil, 750 mg/m/day, days 1-5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients.
According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3'-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027).
ABCC2-24C > T (rs717620), TYMS 3'-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.
本研究旨在探讨基因多态性与多西他赛、顺铂和氟尿嘧啶（DCF）术前化疗治疗食管癌所产生的不良反应之间的关联。
术前DCF（多西他赛，70mg/m²/天，第1天；顺铂，70mg/m²/天，第1天；氟尿嘧啶，750mg/m²/天，第1 - 5天）每3周重复一次，最多进行三个周期。使用入组患者的血样对9种候选基因多态性进行基因分型。
在对50例患者进行的多变量分析中，ABCC2 - 24C/T或T/T基因型（rs717620）的患者更易发生3级或更严重的中性粒细胞减少（OR，5.30，P = 0.013）。此外，TYMS 3'-UTR 0bp/0bp基因型（rs151264360）的患者有发生3级或更严重低钠血症的趋势（OR，0.16，P = 0.005）。TNF-α - 1031C/T或T/T基因型（rs1799964）的患者更易发生2级或更严重的血小板减少（OR，6.30, P = 0.016），IL - 6 - 634C/C基因型（rs1800796）的患者也是如此（OR，0.18，P = 0.034）；MCP - 1 - 2518G/G基因型（rs1024611）的患者更易发生2级或更严重的贫血（OR，0.19，P = 0.027）。
ABCC2 - 24C>T（rs717620）、TYMS ３'-UTR 6-bp插入/缺失（rs151264360）、TNF-α - 1031T>C（rs1799964）以及IL - 6 - 634G>C（rs1800796）和MCP - 1 - 2518A>G（rs1024611）多态性可能分别作为食管癌患者接受多西他赛、顺铂和氟尿嘧啶术前化疗期间中性粒细胞减少、低钠血症、血小板减少和贫血的独立预测生物标志物。
