Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.
Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh.
Cancer Chemother Pharmacol. 2018 Jan;81(1):119-129. doi: 10.1007/s00280-017-3478-3. Epub 2017 Nov 13.
Significant inter-individual variation in the sensitivity to 5-fluorouracil (5-FU) represents a major therapeutic hindrance either by impairing drug response or inducing adverse drug reactions (ADRs). This study aimed at exploring the cause behind this inter-individual alterations in consequences of 5-fluorouracil-based chemotherapy by investigating the effects of DPYD*2A and MTHFR C677T polymorphisms on toxicity and response of 5-FU in Bangladeshi colorectal cancer patients.
Colorectal cancer patients (n = 161) receiving 5-FU-based chemotherapy were prospectively enrolled. DPYD and MTHFR polymorphisms were assessed in peripheral leukocytes. Multivariate analyses were applied to evaluate which variables could predict chemotherapy-induced toxicity and efficacy.
Multivariate analyses showed that DPYD*2A polymorphism was a predictive factor (P = 0.023) for grade 3 and grade 4 5-fluorouracil-related toxicities. Although MTHFR C677T polymorphism might act as forecasters for grade 3 or grade 4 neutropenia, diarrhea, and mucositis, this polymorphism was found to increase significantly (P = 0.006) the response of 5-FU.
DPYD*2A and MTHFR C677T polymorphisms could explain 5-FU toxicity or clinical outcome in Bangladeshi colorectal patients.
5-氟尿嘧啶（5-FU）的敏感性在个体间存在显著差异，这是一个主要的治疗障碍，它要么降低药物反应，要么导致不良反应（ADR）。本研究旨在通过研究 DPYD*2A 和 MTHFR C677T 多态性对孟加拉国结直肠癌患者 5-FU 化疗毒性和反应的影响，探讨导致这种基于 5-FU 的化疗个体间差异的原因。
前瞻性纳入接受 5-FU 为基础的化疗的结直肠癌患者（n=161）。在外周白细胞中评估 DPYD 和 MTHFR 多态性。应用多变量分析评估哪些变量可以预测化疗引起的毒性和疗效。
多变量分析显示，DPYD*2A 多态性是 3 级和 4 级 5-氟尿嘧啶相关毒性的预测因素（P=0.023）。虽然 MTHFR C677T 多态性可能是 3 级或 4 级中性粒细胞减少、腹泻和粘膜炎的预测因子，但该多态性显著增加（P=0.006）5-FU 的反应。
DPYD*2A 和 MTHFR C677T 多态性可以解释孟加拉国结直肠癌患者 5-FU 的毒性或临床结果。
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