Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population
Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population
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DOI：
10.3760/cma.j.issn.0366-6999.2012.05.004
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发表时间：
2012-03-05
影响因子：
6.1
通讯作者：
Wang Shuai
中科院分区：
文献类型：
--
作者：
Zhang Xiao-ping;Bai Zhi-bin;Wang Shuai
背景二氢嘧啶脱氢酶（DPD）是5-氟尿嘧啶（5-FU）催化的关键酶，是研究5-FU药效和毒性的药物遗传学候选基因。本研究旨在探讨二氢嘧啶脱氢酶（DPYD）基因多态性与中国人群中以氟尿嘧啶为基础的辅助化疗的胃癌患者临床预后的关系。采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）技术检测DPYD基因单核苷酸多态性。rs 1801159基因型分布差异有统计学意义（χ 2 =8.76，P=0.012）。纯合基因型rs 1801159 A/A在有反应的患者中比例过高。相反，rs 1801159 A/G基因型携带者在无应答患者中普遍存在。在单倍型关联分析中，各组间单倍型分布差异有统计学意义（χ 2 =3.96，P=0.0465）。结论DPYD基因rs 1801159多态性可作为中国人群胃癌患者氟尿嘧啶化疗疗效的预测指标。设计良好的，全面的，前瞻性的研究，以确定这些多态性DPYD作为预测标志物胃癌的氟尿嘧啶为基础的治疗是必要的。中华医学杂志2012;125（5）：741-746
Background Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.Methods Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.Results The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (chi(2)=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (chi(2)=3.96, P=0.0465).Conclusions These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted. Chin Med J 2012;125(5):741-746