[1] THOMSON MICROMEDEX. MICROMEDEX? Healthcare Series[M/CD] . Vol. 128 expires 6/2006. Colorado： Thomson Micromedex，2006[2006-6-25] . [2] CAI L，ZHU Z. Dihydropyrimidine dehydrogenase(DPD) and its relation with efficacy and toxicity of 5-fluorouracil[J] . Chin Pharm J(中国药学杂志)，2007，42（19）：1441-1445. [3] WEI X，MCLEOD H L，MCMURROUGH J，et al. Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity[J] . J Clin Invest，1996，98(3)：610-615. [4] JOHNSON M R，WANG K，TILLMANNS S，et al. Structural organization of the human dihydropyrimidine dehydrogenase gene[J] . Cancer Res，1997，57(9)：1660-1663. [5] WEI X，ELIZONDO G，SAPONE A，et al. Characterization of the human dihydropyrimidine dehydrogenase gene[J] . Genomics，1998，51(3)：391-400. [6] VAN KUILENBURG A B，VREKEN P，ABELING N G，et al. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency[J] . Hum Genet，1999，104(1)：1-9. [7] VAN KUILENBURG A B，HAASJES J，RICHEL D J，et al. Clinical implications of dihydropyrimidine dehydrogenase (DPD) deficiency in patients with severe 5-fluorouracil-associated toxicity： identification of new mutations in the DPD gene[J] . Clin Cancer Res，2000，6(12)：4705-4712. [8] VAN KUILENBURG A B，BAARS J W，MEINSMA R，et al. Lethal 5-fluorouracil toxicity associated with a novel mutation in the dihydropyrimidine dehydrogenase gene[J] . Ann Oncol，2003，14(2)：341-342. [9] VAN KUILENBURG A B，DOBRITZSCH D，MEINSMA R，et al. Novel disease-causing mutations in the dihydropyrimidine dehydrogenase gene interpreted by analysis of the three-dimensional protein structure[J] . Biochem J，2002，364(Pt 1)：157-163. [10] COLLIE-DUGUID E S，ETIENNE M C，MILANO G，et al. Known variant DPYD alleles do not explain DPD deficiency in cancer patients[J] . Pharmacogenetics，2000，10(3)：217-223. [11] VAN KUILENBURG A B，MEINSMA R，ZOETEKOUW L，et al. High prevalence of the IVS14 + 1G>A mutation in the dihydropyrimidine dehydrogenase gene of patients with severe 5-fluorouracil-associated toxicity[J] . Pharmacogenetics，2002，12(7)：555-558. [12] VAN KUILENBURG A B，MEINSMA R，BEKE E，et al. Identification of three novel mutations in the dihydropyrimidine dehydrogenase gene associated with altered pre-mRNA splicing or protein function[J] . Biol Chem，2005，386(4)：319-324. [13] KOUWAKI M，HAMAJIMA N，SUMI S，et al. Identification of novel mutations in the dihydropyrimidine dehydrogenase gene in a Japanese patient with 5-fluorouracil toxicity[J] . Clin Cancer Res，1998，4(12)：2999-3004. [14] VAN KUILENBURG A B，MEINSMA J R，POLL-THE B T，et al. Identification of a novel disease-causing mutation (100delA) in the dihydropyrimidine dehydrogenase gene[J] . Int Arch Biocsi，2002，1，1096–1100. [15] YAMAGUCHI K，ARAI Y，KANDA Y，et al. Germline mutation of dihydropyrimidine dehydrogenese gene among a Japanese population in relation to toxicity to 5-Fluorouracil[J] . Jpn J Cancer Res，2001，92(3)：337-342. [16] SECK K，RIEMER S，KATES R，et al. Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in a cohort of Caucasian individuals[J] . Clin Cancer Res，2005，11(16)：5886-5892. [17] LAZAR A，JAN WEISSENBORN S，GRUNDEMANN D，et al. Detection of a novel 1905C→T mutation within the dihydropyrimidine dehydrogenase gene and potential for misclassification with the exon 14-skipping mutation[J] . Clin Chem，2003，49(4)：707-708. [18] VREKEN P，VAN KUILENBURG A B，MEINSMA R，et al. Dihydropyrimidine dehydrogenase (DPD) deficiency： identification and expression of missense mutations C29R，R886H and R235W[J] . Hum Genet，1997，101(3)：333-338. [19] PLOYLEARMSAENG S A，FUHR U，JETTER A. How may anticancer chemotherapy with fluorouracil be individualized[J] . Clin Pharmacokinet，2006，45(6)：567-592. [20] OGURA K，OHNUMA T，MINAMIDE Y，et al. Dihydropyrimidine dehydrogenase activity in 150 healthy Japanese volunteers and identification of novel mutations[J] . Clin Cancer Res，2005，11(14)：5104-5111. [21] RIDGE S A，SLUDDEN J，BROWN O，et al. Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects[J] . Br J Clin Pharmacol，1998，46(2)：151-156. [22] SALGUEIRO N，VEIGA I，FRAGOSO M，et al. Mutations in exon 14 of dihydropyrimidine dehydrogenase and 5-Fluorouracil toxicity in Portuguese colorectal cancer patients[J] . Genet Med，2004，6(2)：102-107. [23] RIDGE S A，BROWN O，MCMURROUGH J，et al. Mutations at codon 974 of the DPYD gene are a rare event[J] . Br J Cancer，1997，75(2)：178-179. [24] VREKEN P，VAN KUILENBURG A B，MEINSMA R，et al. Dihydropyrimidine dehydrogenase deficiency： a novel mutation and expression of missense mutations in E. Coli[J] . J Inherit Metab Dis，1998，21(3)：276-279. [25] JIA L，LI J H，CAI J P，et al. Survey of the polymorphism of dihydropyrimidine dehydrogenase gene in the Han nationality population [J] . J China Japan Friendship Hosp(中日友好医院学报)，2005，19（04）：202-207. [26] WEN S Y，WANG X Y，ZHANG M L，et al. Frequency detection of the known DPYD alleles in the studied subjects using oligonucleotide microarray[J] . Prog Biochem Biophys(生物化学与生物物理进展)，2004，31（11）：1031-1037. [27] HSIAO H H，YANG M Y，CHANG J G，et al. Dihydropyrimidine dehydrogenase pharmacogenetics in the Taiwanese population[J] . Cancer Chemother Pharmacol，2004，53(5)：445-451. [28] SUZEN H S，YUCE N，GUVENC G，et al. TYMS and DPYD polymorphisms in a Turkish population[J] . Eur J Clin Pharmacol，2005，61(12)：881-885. [29] CELIK I，KARS A，GUC D，et al. Dihydropyrimidine dehydrogenase enzyme deficiency： clinical and genetic assessment of prevalence in Turkish cancer patients[J] . Cancer Invest，2002，20(3)：333-339. [30] RIDGE S A，SLUDDEN J，WEI X，et al. Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer[J] . Br J Cancer，1998，77(3)：497-500. [31] AHLUWALIA R，FREIMUTH R，MCLEOD H L，et al. Use of pyrosequencing to detect clinically relevant polymorphisms in dihydropyrimidine dehydrogenase[J] . Clin Chem，2003，49(10)：1661-1664. [32] HAMDY S I，HIRATSUKA M，NARAHARA K，et al. Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9，CYP2C19，CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population[J] . Br J Clin Pharmacol，2002，53(6)：596-603. [33] RAIDA M，SCHWABE W，HAUSLER P，et al. Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5′-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)- related toxicity compared with controls[J] . Clin Cancer Res，2001，7(9)：2832-2839. [34] NAUCK M，GIERENS H，MARZ W，et al. Rapid detection of a common dihydropyrimidine dehydrogenase mutation associated with 5-fluorouracil toxicity and congenital thymine uraciluria using fluorogenic hybridization probes[J] . Clin Biochem，2001，34(2)：103-105. [35] VAN KUILENBURG A B，MULLER E W，HAASJES J，et al. Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase (DPD) deficiency after administration of 5-fluorouracil： frequency of the common IVS14+1G>A mutation causing DPD deficiency[J] . Clin Cancer Res，2001，7(5)：1149-1153. [36] CHAZAL M，ETIENNE M C，RENEE N，et al. Link between dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells and liver[J] . Clin Cancer Res，1996，2(3)：507-510. [37] GAMELIN E，BOISDRON-CELLE M，GUERIN-MEYER V，et al. Correlation between uracil and dihydrouracil plasma ratio，fluorouracil (5-FU) pharmacokinetic parameters，and tolerance in patients with advanced colorectal cancer： A potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage[J] . J Clin Oncol，1999，17(4)：1105-1110. [38] JIANG H，LU J，JIANG J，et al. Important role of the dihydrouracil/uracil ratio in marked interpatient variations of fluoropyrimidine pharmacokinetics and pharmacodynamics[J] . J Clin Pharmacol，2004，44(11)：1260-1272. [39] MATTISON L K，EZZELDIN H，CARPENTER M，et al. Rapid identification of dihydropyrimidine dehydrogenase deficiency by using a novel 2-13C-uracil breath test[J] . Clin Cancer Res，2004，10(8)：2652-2658. [40] MATTISON L K，FOURIE J，HIRAO Y，et al. The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity： pharmacokinetic relationship between expired 13CO2 and plasma [2-13C] dihydrouracil[J] . Clin Cancer Res，2006，12(2)：549-555. [41] MAEDA T，SUMI S，HAYASHI K，et al. Automated determination of 5-fluorouracil and its metabolite in urine by high-performance liquid chromatography with column switching[J] . J Chromatogr B Biomed Sci Appl，1999，731(2)：267-273. [42] MARING J G，GROEN H J，WACHTERS F M，et al. Genetic factors influencing pyrimidine-antagonist chemotherapy[J] . Pharmacogenomics，2005，5(4)：226-243.