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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

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Abstract

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 DPYD*2, *3, *4, *12 type mutation, in all patients. Of DPYD*9 gene polymorphism loci in 75 patients, 7 were heterozygote and 68 wild type; of DPYD*5 gene polymorphism loci in 75 patients, 11 were mutation and 23 heterozygote and 41 wild type. The elimination rate constant (Ke) value of DPYD*5 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 DPYD*5 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 DPYD*9 heterozygous genotype than in DPYD*9 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.

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Authors and Affiliations

  1. Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, 31003, Hangzhou, China

    Hong Zhang, You-Ming Li (Professor) & Xi Jin

  2. Clinical Phamarcology, UCB Pharma R&D, B-1420, Braine-l ’Alleud, Belgium

    Hao Zhang

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  1. Hong Zhang
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  2. You-Ming Li
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  3. Hao Zhang
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  4. Xi Jin
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Correspondence to You-Ming Li.

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Zhang, H., Li, YM., Zhang, H. et al. DPYD*5 gene mutation contributes to the reduced DPYD enzyme activity and chemotherapeutic toxicity of 5-FU. Med Oncol 24, 251–258 (2007). https://doi.org/10.1007/BF02698048

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  • DOI: https://doi.org/10.1007/BF02698048

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