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Background  Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene ( DPYD ).    Methods  In this study, we evaluated  DPYD  promoter methylation through quantitative methylation-specific PCR and screened  DPYD  for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity.  DPYD  promoter methylation was also assessed in tumor tissue from 29 patients    Results  Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However,  DPYD  promoter methylation and large  DPYD  intragenic rearrangements were absent in all cases analyzed.    Conclusions  Our results indicate that  DPYD  promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.

bmc cancer

Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients