DPYD*5 gene mutation contributes to the reduced DPYD enzyme activity and chemotherapeutic toxicity of 5-FU: results from genotyping study on 75 gastric carcinoma and colon carcinoma patients.

BACKGROUND

Dihydropyrimidine dehydrogenase (DPYD) plays an important role in the metabolism of 5-FU, which can directly influence the pharmacokinetics and toxicity of 5-FU in patients undergoing chemotherapy. However, little is known of the relationship between DPYD gene polymorphism and metabolism and chemotherapeutic toxicity of 5-FU in gastric carcinoma and colon carcinoma. The present genotyping study demonstrated the relationship between DPYD gene polymorphism among 75 gastric carcinoma and colon carcinoma patients and its impact on 5-FU pharmacokinetic and side effect.

METHODS

We used a chemotherapy scheme based on 5-FU for the treatment of 75 patients with gastrointestinal carcinoma and detected the serum drug concentration and DPYD gene polymorphism (DPYD*2, *3, *4 *5 *9 *12).

RESULTS

We found that there were no DPYD2, 3, 4, 12 type mutation, in all patients. Of DPYD9 gene polymorphism loci in 75 patients, 7 were heterozygote and 68 wild type; of DPYD5 gene polymorphism loci in 75 patients, 11 were mutation and 23 heterozygote and 41 wild type. The elimination rate constant (Ke) value of DPYD5 mutation group was statistically lower than the wild type (p=0.022). The incidence of middle-severe nausea and vomiting and white blood cell decreases in DPYD5 gene type ranging from the highest to lowest can be listed as: mutation, heterozygote, wild type (p<0.05). The incidence of middle-severe nausea and vomiting was significantly higher in DPYD9 heterozygous genotype than in DPYD9 wild genotype (p<0.05).

CONCLUSIONS

DPYD*5 gene mutation contribute to reduced DPYD enzyme activity and 5-FU dysmetabolism, which is associated with the accumulation of 5-FU and the chemotherapeutic toxicity in gastric carcinoma and colon carcinoma.