Authors
Dan Rosmarin, Claire Palles, Alistair Pagnamenta, Kulvinder Kaur, Guillermo Pita, Miguel Martin, Enric Domingo, Angela Jones, Kimberley Howarth, Luke Freeman-Mills, Elaine Johnstone, Haitao Wang, Sharon Love, Claire Scudder, Patrick Julier, Ceres Fernández-Rozadilla, Clara Ruiz-Ponte, Angel Carracedo, Sergi Castellvi-Bel, Antoni Castells, Anna Gonzalez-Neira, Jenny Taylor, Rachel Kerr, David Kerr, Ian Tomlinson
Publication date
2015/1/1
Journal
Gut
Volume
64
Issue
1
Pages
111-120
Publisher
BMJ Publishing Group
Description
Objective
Capecitabine is an oral 5-fluorouracil (5-FU) pro-drug commonly used to treat colorectal carcinoma and other tumours. About 35% of patients experience dose-limiting toxicity. The few proven genetic biomarkers of 5-FU toxicity are rare variants and polymorphisms, respectively, at candidate loci dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthase (TYMS).
Design
We investigated 1456 polymorphisms and rare coding variants near 25 candidate 5-FU pathway genes in 968 UK patients from the QUASAR2 clinical trial.
Results
We identified the first common DPYD polymorphisms to be consistently associated with capecitabine toxicity, rs12132152 (toxicity allele frequency (TAF)=0.031, OR=3.83, p=4.31×10−6) and rs12022243 (TAF=0.196, OR=1.69, p=2.55×10−5). rs12132152 was particularly strongly associated with hand-foot syndrome (OR=6.1, p=3.6×10−8). The rs12132152 and …
Scholar articles
D Rosmarin, C Palles, A Pagnamenta, K Kaur, G Pita… - Gut, 2015