Genetic variation in ST6GAL1 is a determinant of capecitabine and oxaliplatin induced hand-foot syndrome.
Antigens, CD
/ genetics
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Capecitabine
/ adverse effects
Cetuximab
/ therapeutic use
Colorectal Neoplasms
/ drug therapy
Diabetes Mellitus, Type 2
/ complications
Fluorouracil
Genetic Variation
Genome-Wide Association Study
Hand-Foot Syndrome
/ genetics
Humans
Inflammation
/ complications
Oxaliplatin
/ adverse effects
Psoriasis
/ genetics
Sialyltransferases
/ genetics
ST6GAL1
XELOX
chemotherapy
colorectal cancer
genetics
toxicity
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 09 2022
15 09 2022
Historique:
revised:
25
03
2022
received:
09
11
2021
accepted:
28
03
2022
pubmed:
26
4
2022
medline:
28
7
2022
entrez:
25
4
2022
Statut:
ppublish
Résumé
Cancer patients treated with capecitabine and oxaliplatin (XELOX) often develop hand-foot syndrome (HFS) or palmar-plantar erythrodysesthesia. Genetic variation in ST6GAL1 is a risk factor for type-2 diabetes (T2D), a disease also associated with HFS. We analysed genome-wide association data for 10 toxicities in advanced colorectal cancer (CRC) patients from the COIN and COIN-B trials. One thousand and fifty-five patients were treated with XELOX ± cetuximab and 745 with folinic acid, fluorouracil and oxaliplatin ± cetuximab. We also analysed rs6783836 in ST6GAL1 with HFS in CRC patients from QUASAR2. Using UK Biobank data, we sought to confirm an association between ST6GAL1 and T2D (17 384 cases, 317 887 controls) and analysed rs6783836 against markers of diabetes, inflammation and psoriasis. We found that 68% of patients from COIN and COIN-B with grade 2-3 HFS responded to treatment as compared to 58% with grade 0-1 HFS (odds ratio [OR] = 1.1, 95% confidence interval [CI] = 1.02-1.2, P = 2.0 × 10
Identifiants
pubmed: 35467766
doi: 10.1002/ijc.34046
pmc: PMC9545609
doi:
Substances chimiques
Antigens, CD
0
Oxaliplatin
04ZR38536J
Capecitabine
6804DJ8Z9U
Sialyltransferases
EC 2.4.99.-
ST6GAL1 protein, human
EC 2.4.99.1
Cetuximab
PQX0D8J21J
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
957-966Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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