Dihydropyrimidine dehydrogenase enzyme deficiency: Clinical and genetic assessment of prevalence in Turkish cancer patients

Background: Fluorouracil has been reported to induce severe side-effects in particular subjects who have deficiency in dehydropyrimidine dehyrogenase activity, the major enzyme in the catabolism of fluorouracil. Patients and methods: In this study, we aimed to analyze the heterozygote and homozygote frequencies of dehydropyrimidine dehyrogenase gene mutation in 200 patients receiving fluorouracil based chemotherapy together with the assessment of the toxicity profile of these chemotherapy regimens. Results: According to the results of clinical toxicity assessments, grade 3-4 hematologic toxicity was noted in 12% of the patients. Grade 3 gastrointestinal toxicity was present in 5% of the subjects with no grade 4 side effects. The heterozygote (2q(1 - q)) and homozygote (q²) frequencies of dehydropyrimidine dehyrogenase gene mutation were calculated as 1.5% (3/200) and 0.000055% (1/18,043) in the analyzed samples. Conclusion: In this report, for the first time we documented the frequency of dehydropyrimidine dehydrogenase gene mutation in Turkish cancer patients. The determination of enzyme activity in suspected individuals and analysis of other mutations on a population basis would be the next steps for our country.