Objective: To explore the relationship between dihydropyrimidine dehydrogenase (DPYD) gene polymorphism and metabolism as well as chemotherapeutic toxicity of 5-FU in gastric and colonic carcinoma.
Methods: Chemotherapy scheme based on 5-FU was used for the treatment of 75 patients with gastrointestinal carcinoma. Serum drug concentration and DPYD gene polymorphism (DPYD*2, *3, *4, *5, *9, *12) were detected with high performance liquid chromatography (HPLC) and gene chip technique respectively.
Results: It was found that there was no DPYD*2, *3, *4, *12 type mutation in all the patients. Of the DPYD*9 gene polymorphism loci in the 75 patients, there were 7 with heterozygote (9.3%) and 68 with wide type (90.7%). Of the DPYD*5 gene polymorphism loci in the 75 patients, there were 11 with mutation (14.67%) and 23 heterozygote (30.67%) and 41 with wide type (54.67%). Ke value of DPYD*5 mutation was statistically lower than that of wild type (P=0.022). The incidence of middle-severe nausea and vomiting and white blood cell decrease in DPYD*5 gene type could be arranged from the highest to lowest as follows: mutation, heterozygote, wide type (P<0.05). The incidence of middle-severe nausea and vomiting was significantly higher in DPYD*9 heterozygous genotype than in DPYD*9 wild genotype (P<0.05).
Conclusion: DPYD*5 gene mutation contributes to reduced DPYD enzyme activity and 5-FU dyes metabolism, which is associated with accumulation of 5-FU and chemotherapeutic toxicity in patients with gastric and colonic carcinoma.