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 (Po0.001; 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 (Po0.001; 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.
MTHFR, TS and XRCC1 genetic variants may affect survival in patients with myelodysplastic syndromes treated with supportive care or azacitidine / Visani, G.; Loscocco, F.; Ruzzo, A.; Galimberti, S.; Graziano, F.; Voso, M. T.; Giacomini, Emanuele; Finelli, C.; Ciabatti, E.; Fabiani, E.; Barulli, S.; Volpe, A.; Magro, D.; Piccaluga, P.; Fuligni, F.; Vignetti, M.; Fazi, P.; Piciocchi, A.; Gabucci, E.; Rocchi, Marco; Magnani, M.; Isidori, A.. - In: PHARMACOGENOMICS JOURNAL. - ISSN 1470-269X. - 18:3(2018), pp. 444-449. [10.1038/tpj.2017.48]
MTHFR, TS and XRCC1 genetic variants may affect survival in patients with myelodysplastic syndromes treated with supportive care or azacitidine
GIACOMINI, EMANUELE;Vignetti, M.;Fazi, P.;Piciocchi, A.;ROCCHI, Marco;
2018
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 (Po0.001; 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 (Po0.001; 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
