title: Fluoropyrimidine and platinum toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.
abstract: Fluoropyrimidine (FU) and platinum-based chemotherapies are greatly complicated by their associated toxicities. This umbrella systematic review synthesized all systematic reviews that investigated associations between germline variations and toxicity, with the aim of informing personalized medicine. Systematic reviews are important in pharmacogenetics where false positives are common. Four systematic reviews were identified for FU-induced toxicity and three for platinum. Polymorphisms of DPYD and TYMS, but not MTHFR, were statistically significantly associated with FU-induced toxicity (although only DPYD had clinical significance). For platinum, GSTP1 was found to not be associated with toxicity. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of FU and platinum toxicity. It provides a useful reference for clinicians and identifies important research gaps.
authors.affiliation: The Joanna Briggs Institute, Faculty of Health Science, University of Adelaide, Level 1, 115 Grenfell Street, SA 5005, Australia.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Campbell
authors.affiliation: School of Medicine, Faculty of Health Science, University of Adelaide, Frome Road, Adelaide, SA 5000, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Bateman
authors.affiliation: The Joanna Briggs Institute, Faculty of Health Science, University of Adelaide, Level 1, 115 Grenfell Street, SA 5005, Australia.
authors.forename: Micah Dj
authors.initials: MDj
authors.lastname: Peters
authors.affiliation: School of Medicine, Faculty of Health Science, University of Adelaide, Frome Road, Adelaide, SA 5000, Australia.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Bowen
authors.affiliation: School of Medicine, Faculty of Health Science, University of Adelaide, Frome Road, Adelaide, SA 5000, Australia.
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Keefe
authors.affiliation: The Joanna Briggs Institute, Faculty of Health Science, University of Adelaide, Level 1, 115 Grenfell Street, SA 5005, Australia.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Stephenson
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D016190:Carboplatin / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects*; D005472:Fluorouracil / Q000009:adverse effects* / Q000031:analogs & derivatives*; D006801:Humans; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D000078202:Systematic Reviews as Topic
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil
keywords: FU; adverse events; cancer; chemotherapy; fluoropyrimidine; personalized medicine; pharmacogenetics; pharmacogenomics; platinum; toxicity