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

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 o0.001; 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 o0.001; 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.

Influence of MTHFR C677T and A1298C polymorphisms on the survival of pediatric patients with non-Hodgkin lymphoma

“…[16][17][18] However, a recent review concluded that there was no association or opposite effects in the majority of published data, and that these two polymorphisms are not suitable predictors of outcome in pediatric ALL. 5 However, the MTHFR 677TT homozygous genotype has been associated with shorter survival in patients with myelodysplastic syndromes 41 .…”

Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives

“…It has been shown that TS may be involved in the etiopathogenesis of AML. MTHFR c.*177C>G (rs1801133), TS c.*450_*455del (rs11280056) and X-ray repair cross complementing 1 (XRCC1) (DNA repair protein) c.*310A>C (rs25487) mutated alleles have been associated with shorter survival in patients with myelodysplastic syndromes treated with azacitidine versus patients who only received supportive care [ 102 ]. This associated should also be evaluated in AML patients.…”

XRCC1 399GG genotype predicts significantly longer overall survival in resistant lymphoma patients treated with Benda-EAM and ASCT

“…Three single nucleotide polymorphisms (SNPs), XRCC1 rs25487 G/A, XRCC3 rs861539 C/T and ADPRT rs1136410 T/C were analyzed by PCR-RE assay, as previously reported [8]. Primer sequences, preparative PCR conditions and additional details for the RE analysis are reported in Supplementary Table 2.…”

“…Primer sequences, preparative PCR conditions and additional details for the RE analysis are reported in Supplementary Table 2. Statistical analysis was conducted as previously reported [8]. For all the target polymorphisms, the distribution of genotypes was checked for Hardy-Weinberg equilibrium.…”