Dihydropyrimidinase and β-ureidopropionase gene variation and severe fluoropyrimidine-related toxicity

Kummer, Dominic; Fröhlich, Tanja; Joerger, Markus; Aebi, Stefan; Sistonen, Johanna; Amstutz, Ursula; Largiadèr, Carlo Rodolfo (2015). Dihydropyrimidinase and β-ureidopropionase gene variation and severe fluoropyrimidine-related toxicity. Pharmacogenomics, 16(12), pp. 1367-1377. Future Medicine 10.2217/pgs.15.81

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AIMS To assess the association of DPYS and UPB1 genetic variation, encoding the catabolic enzymes downstream of dihydropyrimidine dehydrogenase, with early-onset toxicity from fluoropyrimidine-based chemotherapy. PATIENTS & METHODS The coding and exon-flanking regions of both genes were sequenced in a discovery subset (164 patients). Candidate variants were genotyped in the full cohort of 514 patients. RESULTS & CONCLUSIONS Novel rare deleterious variants in DPYS (c.253C > T and c.1217G > A) were detected once each in toxicity cases and may explain the occurrence of severe toxicity in individual patients, and associations of common variants in DPYS (c.1-1T > C: padjusted = 0.003; OR = 2.53; 95% CI: 1.39-4.62, and c.265-58T > C: padjusted = 0.039; OR = 0.61; 95% CI: 0.38-0.97) with 5-fluorouracil toxicity were replicated.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Fröhlich, Tanja; Aebi, Stefan; Sistonen, Johanna; Amstutz, Ursula and Largiadèr, Carlo Rodolfo

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1462-2416

Publisher:

Future Medicine

Language:

English

Submitter:

Ursula Amstutz

Date Deposited:

03 Nov 2015 14:55

Last Modified:

09 Feb 2018 16:07

Publisher DOI:

10.2217/pgs.15.81

PubMed ID:

26244261

Uncontrolled Keywords:

5-fluorouracil; DPYS; UPB1; capecitabine; dihydropyrimidinase; fluoropyrimidine; gene variation; pharmacogenomics; toxicity; β-ureidopropionase

URI:

https://boris.unibe.ch/id/eprint/72419

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