Evaluating the role of ENOSF1 and TYMS variants as predictors in fluoropyrimidine-related toxicities: an IPD meta-analysis

Publication date: Available online 12 December 2019Source: Pharmacological ResearchAuthor(s): Seid Hamzic, Dominic Kummer, Tanja K. Froehlich, Markus Joerger, Stefan Aebi, Claire Palles, Ian Thomlinson, Didier Meulendijks, Jan H.M. Schellens, Xandra García-González, Luis A. López-Fernández, Ursula Amstutz, Carlo R. LargiadèrAbstractTo 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 ...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research