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.