• Chinese medical journal · Mar 2012

    Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population.

    • Xiao-ping Zhang, Zhi-bin Bai, Bao-an Chen, Ji-feng Feng, Feng Yan, Zhi Jiang, Yue-jiao Zhong, Jian-zhong Wu, Lu Chen, Zu-hong Lu, Na Tong, Zheng-dong Zhang, Pei-pei Xu, Miao-xin Peng, Wen-jing Zhang, and Shuai Wang.
    • Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, China.
    • Chin. Med. J. 2012 Mar 1; 125 (5): 741746741-6.

    BackgroundDihydropyrimidine 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.MethodsThree 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.ResultsThe average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=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 (c2=3.96, P=0.0465).ConclusionsThese 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.

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