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

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.

Nematode response to carbofuran.

Higher populations of Meloidogyne incognita larvae and Pratylenchus penetrans were recovered from soil treated with carbofuran 10 and 15 days after treatment, respectively, than were recovered from untreated control soil. The number of P. penetrans, however, was lower 50 days after treatment, and symptoms developed only occasionally on the root systems of host plants. Populations of Tylenchorhynchus claytoni inoculated at different distances from the base of corn seedlings growing in carbofuran-treated soil did not move toward the plant, whereas they were attracted in untreated soil from a distance of 12 cm. P. penetrans moved at random in treated agar medium when inoculations occurred 4 cm away from the root tips of tomato seedlings under aseptic conditions. Those nematodes that reached the roots were never observed feeding during a 20-day observation period. Specimens of P. penetrans placed on the developing roots moved at random and never penetrated. In contrast, numerous P. penetrans penetrated roots of seedlings growing in untreated medium.