Evaluating the role of ENOSF1 and TYMS variants as predictors in fluoropyrimidine-related toxicities: An IPD meta-analysis
| Autor: | Markus Joerger, Tanja K. Froehlich, Jan H.M. Schellens, Didier Meulendijks, Seid Hamzic, Carlo R. Largiadèr, Claire Palles, Xandra García-González, Luis A. López-Fernández, Ursula Amstutz, Stefan Aebi, Ian Thomlinson, Dominic Kummer |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Antimetabolites Antineoplastic medicine.medical_specialty Multivariate statistics 610 Medicine & health Capecitabine 03 medical and health sciences 0302 clinical medicine Polymorphism (computer science) Neoplasms Internal medicine medicine Humans SNP Allele Hydro-Lyases Pharmacology business.industry Haplotype Cancer Thymidylate Synthase medicine.disease 030104 developmental biology Fluorouracil 030220 oncology & carcinogenesis Hand-Foot Syndrome business medicine.drug |
| Zdroj: | Hamzic, Seid; Kummer, Dominic; Froehlich, Tanja K.; Joerger, Markus; Aebi, Stefan; Palles, Claire; Thomlinson, Ian; Meulendijks, Didier; Schellens, Jan H M; García-González, Xandra; López-Fernández, Luis A; Amstutz, Ursula; Largiadèr, Carlo R. (2020). Evaluating the role of ENOSF1 and TYMS variants as predictors in fluoropyrimidine-related toxicities: An IPD meta-analysis. Pharmacological research, 152, p. 104594. Elsevier 10.1016/j.phrs.2019.104594 |
| ISSN: | 1043-6618 |
| Popis: | To assess the proposed associations of the c.742-227G>A (rs2612091) polymorphism within the Enolase Superfamily Member 1 gene (ENOSF1) and two variants in the adjacent Thymidylate Synthase gene (TYMS): the 5'VNTR 28bp-repeat (rs45445694) and 3'UTR 6bp-indel (rs11280056) with severe toxicity in fluoropyrimidine-treated cancer patients, we performed an individual patient data meta-analysis. Only studies investigating all three-abovementioned variants with fluoropyrimidine-related toxicities were considered for meta-analysis. Associations were tested individually for each study using multivariate regression. Meta-analysis was performed using a random-effects model. One-stage multivariate regressions including tests for independent SNP effects were applied to investigate individual effects of the variants. Multivariate haplotype regression analyses were performed on a pooled dataset to test multi-SNP effects. Of four studies including 2'067 patients, 1'912 were eligible for meta-analysis. All variants were exclusively associated with severe hand-foot-syndrome (HFS) (TYMS 2R: OR = 1.50, p = 0.0002; TYMS 6bp-ins: OR = 1.42 p = 0.0036; ENOSF1 c.742-227G: OR = 1.64 p A and the TYMS 28bp-repeat: each toxicity-associated allele increased the risk for severe HFS (OR = 1.32 per allele, p |
| Databáze: | OpenAIRE |
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