title: Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population.
abstract: 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 (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).
  
  
  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.
authors.affiliation: Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Zhang
authors.forename: Zhi-bin
authors.initials: ZB
authors.lastname: Bai
authors.forename: Bao-an
authors.initials: BA
authors.lastname: Chen
authors.forename: Ji-feng
authors.initials: JF
authors.lastname: Feng
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Zhi
authors.initials: Z
authors.lastname: Jiang
authors.forename: Yue-jiao
authors.initials: YJ
authors.lastname: Zhong
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Wu
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Zu-hong
authors.initials: ZH
authors.lastname: Lu
authors.forename: Na
authors.initials: N
authors.lastname: Tong
authors.forename: Zheng-dong
authors.initials: ZD
authors.lastname: Zhang
authors.forename: Pei-pei
authors.initials: PP
authors.lastname: Xu
authors.forename: Miao-xin
authors.initials: MX
authors.lastname: Peng
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil