Genetic variation in ST6GAL1 is a determinant of capecitabine and oxaliplatin induced hand-foot syndrome.

Autor: Watts K; Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK., Wills C; Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK., Madi A; The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK., Palles C; Institute of Cancer and Genomic Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham, UK., Maughan TS; CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK., Kaplan R; MRC Clinical Trials Unit, University College of London, London, UK., Al-Tassan NA; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Kerr R; Department of Oncology, Old Road Campus Research Building, University of Oxford, Oxford, UK., Kerr DJ; Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK., Houlston RS; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Escott-Price V; Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK., Cheadle JP; Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2022 Sep 15; Vol. 151 (6), pp. 957-966. Date of Electronic Publication: 2022 May 10.
DOI: 10.1002/ijc.34046
Abstrakt: 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 -4 ). HFS was also associated with improved overall survival (hazard ratio = 0.92, 95% CI = 0.84-0.99, P = 4.6 × 10 -2 ). rs6783836 at ST6GAL1 was associated with HFS in patients treated with XELOX (OR = 3.1, 95% CI = 2.1-4.6, P = 4.3 × 10 -8 ) and was borderline significant in patients receiving capecitabine from QUASAR2, but with an opposite allele effect (OR = 0.66, 95% CI = 0.42-1.03, P = .05). ST6GAL1 was associated with T2D (lead SNP rs3887925, OR = 0.94, 95% CI = 0.92-0.96, P = 1.2 × 10 -8 ) and the rs6783836-T allele was associated with lowered HbA1c levels (P = 5.9 × 10 -3 ) and lymphocyte count (P = 2.7 × 10 -3 ), and psoriasis (P = 7.5 × 10 -3 ) beyond thresholds for multiple testing. In conclusion, HFS is a biomarker of treatment outcome and rs6783836 in ST6GAL1 is a potential biomarker for HFS with links to T2D and inflammation.
(© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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