MTHFR, TS and XRCC1 genetic variants may affect survival in patients with myelodysplastic syndromes treated with supportive care or azacitidine.
Pharmacogenomics J
; 18(3): 444-449, 2018 05 22.
Article
in En
| MEDLINE
| ID: mdl-29205204
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thymidylate Synthase
/
Myelodysplastic Syndromes
/
Methylenetetrahydrofolate Reductase (NADPH2)
/
X-ray Repair Cross Complementing Protein 1
Type of study:
Prognostic_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Pharmacogenomics J
Journal subject:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Year:
2018
Type:
Article
Affiliation country:
Italy