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MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin

The Pharmacogenomics Journal volume 15, pages 219–225 (2015)Cite this article

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Abstract

Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases. 5,10-Methylentetrahydrofolate reductase (MTHFR) MTHFR-1298 A>C (rs1801131) polymorphism had a concordant effect: MTHFR-rs1801131-1298CC genotype carriers had a worse disease free survival (DFS) in both the cohorts. In the pooled population MTHFR-rs1801131-1298CC carriers had also a worse overall survival. We computed a clinical score related to DFS including MTHFR-rs1801131, tumor stage, sex and tumor location, where rs1801131 is the most detrimental factor (hazard ratio=5.3, 95% confidence interval=2.2–12.9; P-value=0.0006). MTHFR-rs1801131 is a prognostic factor that could be used as an additional criteria for the choice of the proper adjuvant regimen in stage II/III colorectal cancer patients.

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Acknowledgements

This work was supported by the ‘Associazione ABO per l’Applicazione delle Biotecnologie in Oncologia’ to GT; the ‘Associazione Italiana per la Ricerca sul Cancro (AIRC) (Special Program Molecular Clinical Oncology, 5 × 1000, (No. 12214)) to GT; the European Research Council (Programme ‘ideas’, Proposal No 269051’) to GT; the Italian Ministry of Education MIUR (FIRB prot. RBAP11ETKA) to GT; Ente Cassa di Risparmio di Firenze to EM; Associazione Giacomo Onlus, Castiglioncello to EM; and Gruppo Oncologico Chirurgico Cooperativo Italiano, Florence to EM.

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Authors and Affiliations

  1. Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico- National Cancer Institute, Aviano, Italy

    E Cecchin, E De Mattia, C Zanusso, F Rizzolio & G Toffoli

  2. Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy

    G Perrone, S Nobili, P Petreni, T Mazzei & I Landini

  3. Epidemiology and Biostatistics Unit, Centro di Riferimento Oncologico- National Cancer Institute, via Franco Gallini, Aviano, Italy

    J Polesel

  4. Medical Oncology Unit 1, Istituto Oncologico Veneto- IRCCS, Padua, Italy

    S Lonardi

  5. Medical Oncology Unit, University Hospital, Piazza S. Maria Della Misericordia, Udine, Italy

    N Pella

  6. Medical Oncology Unit, ‘San Filippo Neri Hospital’, Piazza Di S. Maria Della Pieta', Rome, Italy

    M D'Andrea

  7. Medical Oncology Unit, Ospedale Civile di Vittorio Veneto, Vittorio, Veneto (TV), Italy

    D Errante

  8. Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy

    E Mini

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Cecchin, E., Perrone, G., Nobili, S. et al. MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin. Pharmacogenomics J 15, 219–225 (2015). https://doi.org/10.1038/tpj.2014.64

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