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

摘要

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 (x2=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 (x2=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.