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DPYD IVS14+1G>A and 2846A>T genotyping for the prediction of severe fluoropyrimidine-related toxicity: a meta-analysis

    Salvatore Terrazzino

    * Author for correspondence

    Università del Piemonte Orientale “A. Avogadro”, Dipartimento di Scienze del Farmaco & Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Largo Donegani 2, 28100 Novara, Italy.

    ,
    Sarah Cargnin

    Università del Piemonte Orientale “A. Avogadro”, Dipartimento di Scienze del Farmaco & Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Largo Donegani 2, 28100 Novara, Italy

    ,
    Marzia Del Re

    Divisione di Farmacologia, Dipartimento di Medicina Sperimentale e Clinica, Università di Pisa, Italy

    ,
    Romano Danesi

    Divisione di Farmacologia, Dipartimento di Medicina Sperimentale e Clinica, Università di Pisa, Italy

    ,
    Pier Luigi Canonico

    Università del Piemonte Orientale “A. Avogadro”, Dipartimento di Scienze del Farmaco & Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Largo Donegani 2, 28100 Novara, Italy

    &
    Armando A Genazzani

    Università del Piemonte Orientale “A. Avogadro”, Dipartimento di Scienze del Farmaco & Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Largo Donegani 2, 28100 Novara, Italy

    Published Online:https://doi.org/10.2217/pgs.13.116

    Aim: In the present study we conducted a systematic review and meta-analysis of published data to quantify the impact of the DPYD IVS14+1G>A and 2846A>T variants on the risk of fluoropyrimidine-related toxicities and to determine sensitivity and specificity testing for DPYD variants. Methods: Relevant studies were identified through PubMed and Web of Knowledge databases, studies included were those published up until to May 2012. Study quality was assessed according to the HuGENET guidelines and Strengthening the Reporting of Genetic Association (STREGA) recommendations. Results: Random-effects meta-analysis provided evidence that carriers of DPYD IVS14+1G>A are at higher risk of ≥3 degrees of overall grade toxicity, hematological toxicity, mucositis and diarrhea. In addition, a strong association was also found between carriers of the DPYD 2846T allele and overall grade ≥3 toxicity or grade ≥3 diarrhea. An inverse linear relationship was found in prospective studies between the odds ratio of DPYD IVS14+1G>A and the incidence of overall grade ≥3 toxicity, indicating an higher impact in cohorts in which the incidence of severe toxicity was lower. Conclusion: The results of this meta-analysis confirm clinical validity of DPYD IVS14+1G>A and 2846A>T as risk factors for the development of severe toxicities following fluoropyrimidine treatment. Furthermore, the sensitivity and specificity estimates obtained could be useful in establishing the cost–effectiveness of testing for DPYD variants.

    Original submitted 4 March 2013; Revision submitted 17 June 2013

    Papers of special note have been highlighted as: ▪ of interest

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