Additional genetic risk factor for death in children with acute lymphoblastic leukemia: a common polymorphism of the MTHFR gene.
BACKGROUND
The presence of metabolically important genetic polymorphisms may affect treatment efficacy in patients with malignancies. The objective of this prospective multicenter study was to evaluate the role of selected polymorphisms of genes associated with metabolism of chemotherapeutic drugs as prognostic markers in children with acute lymphoblastic leukemia.


METHODS
Genotyping for the presence of 7 genetic variants in 403 patients and analysis of death cases were performed.


RESULTS
Thirty-one children died before reaching remission maintenance phase. Genetic analysis revealed in this group increased frequency of homozygosity for c.677C>T polymorphism of the MTHFR gene (26% vs. 8% in the survivors; OR 4.09; 95% CI 1.67-10; adjusted for multiple testing P = 0.028).


CONCLUSIONS
Our data suggest that modification of anti-leukemic treatment should be considered in patients homozygous for c.677C>T polymorphism.
Pietrzyk
Jacek J
JJ
Chair of Pediatrics, Jagiellonian University, Krakow, Poland.
Bik-Multanowski
Miroslaw
M
Balwierz
Walentyna
W
Skoczen
Szymon
S
Wojcik
Dorota
D
Chybicka
Alicja
A
Sikorska-Fic
Barbara
B
Matysiak
Michal
M
Szczepanski
Tomasz
T
Sonta-Jakimczyk
Danuta
D
Ploszynska
Anna
A
Balcerska
Anna
A
Mycko
Katarzyna
K
Bodalski
Jerzy
J
Krawczuk-Rybak
Maryna
M
Kowalczyk
Jerzy
J
Koltan
Andrzej
A
Sobol
Grazyna
G
Derwich
Katarzyna
K
Kwinta
Przemko
P
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2) / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality*; D012307:Risk Factors
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2)