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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-05-22

AUTHORS

G Visani, F Loscocco, A Ruzzo, S Galimberti, F Graziano, M T Voso, E Giacomini, C Finelli, E Ciabatti, E Fabiani, S Barulli, A Volpe, D Magro, P Piccaluga, F Fuligni, M Vignetti, P Fazi, A Piciocchi, E Gabucci, M Rocchi, M Magnani, A Isidori

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. More... »

PAGES

444

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/tpj.2017.48

DOI

http://dx.doi.org/10.1038/tpj.2017.48

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1095858627

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29205204


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