Germline pharmacogenomics of DPYD*9A (c.85T>C) variant in patients with gastrointestinal malignancies treated with fluoropyrimidines

Moh'd Khushman, Girijesh Kumar Patel, Peter Joel Hosein, Javier Ariel Laurini, Daniel Cameron, David Roland Clarkson, Thomas Wayne Butler, Carole Wiseman Norden, Wilma Baliem, Vanessa Jones, Sanjyot Bhadkamkar, Cindy Nelson, Frances Lee, Ajay P. Singh, William R. Taylor

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Background: The correlation between DPYD*9A (c.85T>C) genotype and dihydropyrimidine dehydrogenase (DPD) deficiency clinical phenotype is controversial. Reference laboratories either did not perform DPYD*9A genotyping or have stopped DPYD*9A genotyping and limited genotyping to high-risk variants (DPYD*2A, DPYD*13 and DPYD*9B) only. This study explored DPYD*9A genotype and clinical phenotype correlation in patients with gastrointestinal (GI) malignancies treated with fluoropyrimidines. Methods: Between 2011 and 2017, 67 patients with GI malignancies were genotyped for DPYD variants. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Fisher's exact test was used for statistical analysis. Results: DPYD variants were identified in 17 out of 67 (25%) patients. One patient was homozygous for DPYD*9A variant and one patient was double heterozygous for DPYD*9A and DPYD*9B variants. In patients with identified DPYD variants, 13/17 (76%) patients had DPYD*9A variant, 3/17 (18%) patients had DPYD*2A variant and 2/17 (12%) patient had DPYD*9B variant. Only patients genotyped prior to 2015 were genotyped for DPYD*9A variant (N=28). Of those, 13/28 patients (46%) had DPYD*9A variant. Grade 3-4 diarrhea was associated with DPYD*9A variant in patients treated with full dose fluoropyrimidines (P=0.0055). Conclusions: In our cohort, DPYD*9A variant was the most common diagnosed variant. The correlation between DPYD*9A genotype and DPD deficiency in clinical phenotype was noticeable in patients who received full dose fluoropyrimidines as they all experienced grade 3-4 toxicities (diarrhea).

Original languageEnglish
Pages (from-to)416-424
Number of pages9
JournalJournal of Gastrointestinal Oncology
Issue number3
StatePublished - Jun 1 2018


  • 9A (c.85T>C) variant
  • DPYD
  • Dihydropyrimidine dehydrogenase (DPD)
  • Fluorouracil (FU)
  • Gastrointestinal malignancy
  • Germline pharmacogenomics


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