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2010-07-13

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126302

UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy

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https://doi.org/10.1038/sj.bjc.6605776

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BACKGROUND: The impact of thymidylate synthase (TYMS) and UDP-glucoronosyltransferase 1A (UGT1A) germline polymorphisms on the outcome of colorectal cancer (CRC) patients treated with irinotecan plus 5-fluorouracil (irinotecan/5FU) is still controversial. Our objective was to define a genetic-based algorithm to select patients to be treated with irinotecan/5FU. METHODS: Genotyping of TYMS (5'TRP and 3'UTR), UGT1A1*28, UGT1A9*22 and UGT1A7*3 was performed in 149 metastatic CRC patients treated with irinotecan/5FU as first-line chemotherapy enrolled in a randomised phase 3 study. Their association with response, toxicity and survival was investigated by univariate and multivariate statistical analysis. RESULTS: TYMS 3TRP/3TRP genotype was the only independent predictor of tumour response (OR=5.87, 95% confidence interval (CI)=1.68-20.45; P=0.005). UGT1A1*28/*28 was predictive for haematologic toxicity (OR=6.27, 95% CI=1.09-36.12; P=0.04), specifically for neutropenia alone (OR=6.40, 95% CI=1.11-37.03; P=0.038) or together with diarrhoea (OR=18.87, 95% CI=2.14-166.67; P=0.008). UGT1A9*1/*1 was associated with non-haematologic toxicity (OR=2.70, 95% CI=1.07-6.82; P=0.035). Haplotype VII (all non-favourable alleles) was associated with non-haematologic toxicity (OR=2.11, 95% CI-1.12-3.98; P-0.02). CONCLUSION: TYMS and UGT1A polymorphisms influence on tumour response and toxicities derived from irinotecan/5FU treatment in CRC patients. A genetic-based algorithm to optimise treatment individualisation is proposed. British Journal of Cancer (2010) 103, 581-589. doi:10.1038/sj.bjc.6605776 www.bjcancer.com Published online 13 July 2010 (C) 2010 Cancer Research UK

Matèries

Càncer colorectal, Toxicitat dels medicaments

Matèries (anglès)

Colorectal cancer, Drug toxicity

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Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

MARTÍNEZ BALIBREA, Eva, ABAD, Albert, MARTÍNEZ CARDÚS, Anna, GINÉS, A., VALLADARES, M., NAVARRO, M., ARANDA, Enrique, MARCUELLO, Eugenio, BENAVIDES, M., MASSUTÍ, B., CARRATO, A., LAYOS, Laura, MANZANO, José luis, MORENO AGUADO, Víctor. UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy. _British Journal of Cancer_. 2010. Vol. 103, núm. 4, pàgs. 581-589. [consulta: 23 de gener de 2026]. ISSN: 0007-0920. [Disponible a: https://hdl.handle.net/2445/126302]

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