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Acute Leukemias

Role of MTHFR (677, 1298) haplotype in the risk of developing secondary leukemia after treatment of breast cancer and hematological malignancies

Leukemia volume 21, pages 1413–1422 (2007)Cite this article

Abstract

Therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) is a malignancy occurring after exposure to chemotherapy and/or radiotherapy. Polymorphisms involved in chemotherapy/radiotherapy response genes could be related to an increased risk of developing this neoplasia. We have studied 11 polymorphisms in genes of drug detoxification pathways (NQO1, glutathione S-transferase pi) and DNA repair xeroderma pigmentosum, complementation group (3) (XPC(3), X-ray repair cross complementing protein (1)), Nijmegen breakage syndrome (1), excision repair cross-complementing rodent repair deficiency, complementation group (5) and X-ray repair cross complementing protein (3) and in the methylene tetrahydrofolate reductase gene (MTHFR(2), 677C>T, 1298A>C), involved in DNA synthesis. The analyzed groups were a t-MDS/AML patients group (n=81) and a matched control group (n=64) treated similarly, and they did not develop t-MDS/AML. We found no significant differences when the groups were compared globally. However, when analysis was carried out according to the primary neoplasia involved, a significant association was observed between the MTHFR haplotype (single nucleotide polymorphisms 677 and 1298) and the risk of developing t-MDS/AML in the breast cancer patients group (P=0.016) and cyclophosphamide-treated hematological disease group (P=0.005). Risk haplotype was different for each case, corresponding to the 677T1298A haplotype after breast cancer treatment and the 677C1298C haplotype after hematological malignancy treatment. We postulate that such differences are related to variations in chemotherapy schemes between hematological and breast cancers and their differential interaction with the MTHFR route.

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Acknowledgements

The present study was financially supported by the Spanish Instituto de Salud Carlos III. Networks of groups. FIS G03-008 and PI050763 projects.

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Authors and Affiliations

  1. Servicio de Hematología y Oncología, Hospital Clínico Universitario de Valencia, Universidad de Valencia, Valencia, Spain

    V M Guillem, M Collado, M J Terol, A Lluch & M Tormo

  2. Departamento de Genética, Universidad de Navarra, Pamplona, Spain

    M J Calasanz

  3. Servicio de Hematología, Hospital Clínic de Barcelona, Barcelona, Spain

    J Esteve

  4. Servicio de Hematología, Hospital Clínico Universitario de Salamanca, Salamanca, Spain

    M Gonzalez

  5. Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain

    C Sanzo

  6. Servicio de Hematología, Hospital Sant Pau, Barcelona, Spain

    J Nomdedeu

  7. Laboratorio de Biología Molecular, Hospital Universitario La Fe, Valencia, Spain

    P Bolufer

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  1. V M Guillem
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Correspondence to M Tormo.

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Guillem, V., Collado, M., Terol, M. et al. Role of MTHFR (677, 1298) haplotype in the risk of developing secondary leukemia after treatment of breast cancer and hematological malignancies. Leukemia 21, 1413–1422 (2007). https://doi.org/10.1038/sj.leu.2404709

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