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Single-nucleotide polymorphisms of DPYD predict adverse events associated with 5-fluorouracil in patients with gastrointestinal cancer

Date

19 Dec 2015

Session

Poster presentation 1

Presenters

Shinobu Ohnuma

Citation

Annals of Oncology (2015) 26 (suppl_9): 8-15. 10.1093/annonc/mdv518

Authors

S. Ohnuma1, M. Toshima2, K. Miura1, K. Kudoh2, M. Ishida1, H. Karasawa1, H. Musha1, F. Motoi2, T. Naitoh1, M. Unno2

Author affiliations

  • 1 Department Of Surgery, Tohoku University Hospital, 980-8574 - Sendai/JP
  • 2 Department Of Surgery, Tohoku University Hospital, Sendai/JP
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Aim/Background

The aim of this study was to investigate the association between 5-fluorouracil (5-FU)-related adverse events (AEs) in Japanese patients with gastrointestinal cancer treated with 5-FU and the patients genotypes of DPYD.

Methods

Sequence analyses of 20 polymorphisms in DPYD were performed using genomic DNA extracted from peripheral blood mononuclear cells of 103 patients with gastric (n = 34) or colorectal (n = 69) cancer. The 5-FU-related AEs of in these 103 patients were evaluated based on the medical records of patients in each of three groups: the intravenous administration group (i.v. group, n = 51), oral administration group (p.o. group, n = 106), and all-regimens group (both i.v. and p.o. group, n = 157). The associations between the incidence of AEs and each genotype were statistically analyzed.

Results

Three single-nucleotide polymorphisms (SNPs) of DPYD were identified; c.496A > G (n = 7), c.1905 + 1G > A (n = 1), and c.2303C > A (n = 3), those of which were all heterozygote. Among them, five of seven c.496A > G individuals suffered from grade 3 neutropenia (n = 1), fatigue (n = 3), and diarrhea (n = 2). One of three c.2303C > A individuals suffered from grade 3 neutropenia and fatigue. The one c.1905 + 1G > A individual suffered from grade 4 neutropenia and grade 3 hyperbilirubinemia. The patients in the all-regimens group carrying any one of three DPYD SNPs showed statistically significant associations with the incidence of AEs of any type and fatigue. A similar trend was observed in the p.o. group, but not in the i.v. group.

Conclusions

These findings suggest that the DPYD SNPs c.496A > G, c.1905 + 1G > A, and c.2303C > A might be predictive factors for the occurrence of severe 5-FU-related AEs.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.

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