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

作者：Visani G.; Loscocco F.; Ruzzo A.; Galimberti S.; Graziano F.; Voso M. T.; Giacomini E.; 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 M.; Magnani M.; Isidori A.

来源：The Pharmacogenomics Journal, 2018, 18(3): 444-449.

DOI：10.1038/tpj.2017.48

We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myeloddysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677TTF, thymidyiate 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; = 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.

• 出版日期2018-5-22