Sequence Analysis of the 5′-Flanking Regions of Human Dihydropyrimidine Dehydrogenase Gene: Identification of a New Polymorphism Related with Effects of 5-Fluorouracil

Dihydropyrimidine dehydrogenase (DPD), known as a rate-limiting metabolic enzyme in the catabolism of 5-fluorouracil (5-FU), degrades more than about 80% of the administered 5-FU in human liver. Since it was reported that the anticancer effects of 5-FU were observed in cancer patients with lower DPD activities, many attempts have been conducted to anticipate the expected anticancer effects of 5-FU based on expression of intracanceral DPD. It have been reported that 39 different mutations and polymorphisms in the coding regions of DPD genes have been identified; however, there is no report on polymorphisms in the 5′-flanking region of DPD genes. We investigated polymorphisms in the 5′-flanking regions (3,058 bp), which are considered to control expression of DPD genes, in genomic DNA extracted from 37 kinds of human cancer cells. As the results, out of 37 cancer cells subjected to analysis, DLD-1 cells had C insertion and 7 strains G deletion, which were hetelozygote. No significant relationship was identi...