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 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.
Zhang
Hong
H
Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 31003, China.
Li
You-ming
YM
Zhang
Hao
H
Jin
Xi
X
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil