1. ¹Servicio de Hematología y Oncología, Hospital Clínico Universitario de Valencia, Universidad de Valencia, Valencia, Spain
2. ²Departamento de Genética, Universidad de Navarra, Pamplona, Spain
3. ³Servicio de Hematología, Hospital Clínic de Barcelona, Barcelona, Spain
4. ⁴Servicio de Hematología, Hospital Clínico Universitario de Salamanca, Salamanca, Spain
5. ⁵Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain
6. ⁶Servicio de Hematología, Hospital Sant Pau, Barcelona, Spain
7. ⁷Laboratorio de Biología Molecular, Hospital Universitario La Fe, Valencia, Spain

Correspondence: Dr M Tormo Díaz, Servicio de Hematología y Oncología, Hospital Clínico Universitario de Valencia, Avda Blasco Ibáñez, 17, Valencia 46010, Spain. E-mail: tormo_mar@gva.es

Received 1 December 2006; Revised 13 March 2007; Accepted 16 March 2007; Published online 3 May 2007.

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.