TY - JOUR
T1 - Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia
AU - De Jonge, Robert
AU - Tissing, Wim J.E.
AU - Hooijberg, Jan Hendrik
AU - Jansen, Gerrit
AU - Kaspers, Gertjan J.L.
AU - Lindemans, Jan
AU - Peters, Godefridus J.
AU - Pieters, Rob
PY - 2009/3/5
Y1 - 2009/3/5
N2 - Polymorphisms in folate pathway genes may influence the susceptibility to acute lymphoblastic leukemia (ALL). DNA was isolated from 245 pediatric ALL patients (cases) and from 500 blood bank donors (controls). Polymorphisms in methylene-tetrahydrofolate reductase (MTHFR677C>T,1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), nicotinamide N-methyltransferase (NNMT IVS-151C>T), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC1 80G>A) were detected. In ALL patients, an increased occurrence was observed of the RFC1 80AA variant (odds ratio[OR] = 2.1; 95% confidence interval[CI] = 1.3-3.2; P =.002) and the RFC1 80A allele (OR = 1.5; 95% CI, 1.1-2.1; P =.02). Likewise, the NNMT IVS-151TT genotype showed a 2.2-fold increased ALL risk (OR = 2.2; 95% CI, 1.1-4.6; P =.04). A 1.4-fold reduction in ALL risk was observed for (heterozygous or homozygous) carriers of the TS 2R allele and the MTHFR 677T allele (OR = 0.7; 95% CI, 0.5-1.0; P <.05). Furthermore, interactions between NNMT and MTHFR 677C>T and RFC were observed. NNMT IVS-151CC/MTHFR 677CT + TT patients exhibited a 2-fold reduction in ALL risk whereas RFC1 80AA/NNMT IVS-151CT + TT subjects had a 4.2-fold increase in ALL risk (P =.001). For the first time, we associate the RFC1 80G>A and NNMT IVS-151C> T variants to an increased ALL susceptibility.(Blood. 2009;113:2284-2289)
AB - Polymorphisms in folate pathway genes may influence the susceptibility to acute lymphoblastic leukemia (ALL). DNA was isolated from 245 pediatric ALL patients (cases) and from 500 blood bank donors (controls). Polymorphisms in methylene-tetrahydrofolate reductase (MTHFR677C>T,1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), nicotinamide N-methyltransferase (NNMT IVS-151C>T), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC1 80G>A) were detected. In ALL patients, an increased occurrence was observed of the RFC1 80AA variant (odds ratio[OR] = 2.1; 95% confidence interval[CI] = 1.3-3.2; P =.002) and the RFC1 80A allele (OR = 1.5; 95% CI, 1.1-2.1; P =.02). Likewise, the NNMT IVS-151TT genotype showed a 2.2-fold increased ALL risk (OR = 2.2; 95% CI, 1.1-4.6; P =.04). A 1.4-fold reduction in ALL risk was observed for (heterozygous or homozygous) carriers of the TS 2R allele and the MTHFR 677T allele (OR = 0.7; 95% CI, 0.5-1.0; P <.05). Furthermore, interactions between NNMT and MTHFR 677C>T and RFC were observed. NNMT IVS-151CC/MTHFR 677CT + TT patients exhibited a 2-fold reduction in ALL risk whereas RFC1 80AA/NNMT IVS-151CT + TT subjects had a 4.2-fold increase in ALL risk (P =.001). For the first time, we associate the RFC1 80G>A and NNMT IVS-151C> T variants to an increased ALL susceptibility.(Blood. 2009;113:2284-2289)
UR - http://www.scopus.com/inward/record.url?scp=64049110710&partnerID=8YFLogxK
U2 - 10.1182/blood-2008-07-165928
DO - 10.1182/blood-2008-07-165928
M3 - Article
C2 - 19020309
AN - SCOPUS:64049110710
SN - 0006-4971
VL - 113
SP - 2284
EP - 2289
JO - Blood
JF - Blood
IS - 10
ER -