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MTHFR, TS and XRCC1 genetic variants may affect survival in patients with myelodysplastic syndromes treated with supportive care or azacitidine.

Hematology and Hematopoietic Stem Cell Transplant Center, AORMN, Pesaro, Italy. Department of Biomolecular Sciences, Section of Biotechnologies, University of Urbino 'Carlo Bo', Urbino, Italy. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. Hematology Unit, Tor Vergata University, Rome, Italy. Department of Hematology, S. Orsola-Malpighi Hospital, Bologna, Italy. Hematology and Transplant Center, S. Giuseppe Moscati Hospital, Avellino, Italy. Hematology Unit, Pugliese-Ciacco Hospital, Catanzaro, Italy. Hematopathology Section, Department of Experimental, Diagnostic, and Specialty Medicine, S. Orsola-Malpighi Hospital, Bologna University, Bologna, Italy. Fondazione GIMEMA, Rome, Italy. Institute of Biomathematics, University of Urbino 'Carlo Bo', Urbino, Italy.

The pharmacogenomics journal. 2018;(3):444-449
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Abstract

We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'-untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and short survival was found in patients receiving BSC by multivariate analysis (P<0.001; P=0.026; P=0.058; P=0.024). MTHFR 677T/T, TS 3'-UTR -6 bp/-6 bp and XRCC1 399G/G genotypes were associated with short survival in patients receiving azacitidine by multivariate analysis (P<0.001; P=0.004; P=0.002). We then performed an exploratory analysis to evaluate the effect of the simultaneous presence of multiple adverse variant genotypes. Interestingly, patients with ⩾1 adverse genetic variants had a short survival, independently from their International Prognostic Scoring System (IPSS) and therapy received. To our knowledge, this is the first study showing that polymorphisms in folate-metabolizing pathway, DNA synthesis and DNA repair genes could influence survival of MDS patients.