PMID- 10536004
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 22
DP  - 1999 Oct 26
TI  - Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with
      susceptibility to acute leukemia in adults.
PG  - 12810-5
AB  - Reduction of 5,10-methylenetetrahydrofolate (methyleneTHF), a donor for
      methylating dUMP to dTMP in DNA synthesis, to 5-methyltetrahydrofolate
      (methylTHF), the primary methyl donor for methionine synthesis, is catalyzed by
      5,10-methylenetetrahydrofolate reductase (MTHFR). A common 677 C --> T
      polymorphism in the MTHFR gene results in thermolability and reduced MTHFR
      activity that decreases the pool of methylTHF and increases the pool of
      methyleneTHF. Recently, another polymorphism in MTHFR (1298 A --> C) has been
      identified that also results in diminished enzyme activity. We tested whether
      carriers of these variant alleles are protected from adult acute leukemia. We
      analyzed DNA from a case-control study in the United Kingdom of 308 adult acute
      leukemia patients and 491 age- and sex-matched controls. MTHFR variant alleles
      were determined by a PCR-restriction fragment length polymorphism assay. The
      MTHFR 677TT genotype was lower among 71 acute lymphocytic leukemia (ALL) cases
      compared with 114 controls, conferring a 4.3-fold decrease in risk of ALL [odds
      ratio (OR = 0.23; 95% CI = 0.06-0.81]. We observed a 3-fold reduction in risk of 
      ALL in individuals with the MTHFR 1298AC polymorphism (OR = 0.33; 95% CI =
      0.15-0.73) and a 14-fold decreased risk of ALL in those with the MTHFR 1298CC
      variant allele (OR = 0.07; 95% CI = 0.00-1.77). In acute myeloid leukemia, no
      significant difference in MTHFR 677 and 1298 genotype frequencies was observed
      between 237 cases and 377 controls. Individuals with the MTHFR 677TT, 1298AC, and
      1298CC genotypes have a decreased risk of adult ALL, but not acute myeloid
      leukemia, which suggests that folate inadequacy may play a key role in the
      development of ALL.
FAU - Skibola, C F
AU  - Skibola CF
AD  - School of Public Health, University of California, Berkeley, CA 94720, USA.
      martynts@uclink4.berkeley.edu
FAU - Smith, M T
AU  - Smith MT
FAU - Kane, E
AU  - Kane E
FAU - Roman, E
AU  - Roman E
FAU - Rollinson, S
AU  - Rollinson S
FAU - Cartwright, R A
AU  - Cartwright RA
FAU - Morgan, G
AU  - Morgan G
LA  - eng
GR  - P30 ES001896/ES/NIEHS NIH HHS/United States
GR  - P42 ES004705/ES/NIEHS NIH HHS/United States
GR  - P30ES01896/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA Primers)
RN  - EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
CIN - Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12216-8. PMID: 10535898
MH  - Acute Disease
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Base Sequence
MH  - DNA Primers
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Leukemia/*enzymology/genetics
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)
MH  - Middle Aged
MH  - Oxidoreductases Acting on CH-NH Group Donors/*genetics
MH  - *Polymorphism, Genetic
PMC - PMC23109
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - 10.1073/pnas.96.22.12810 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12810-5. doi:
      10.1073/pnas.96.22.12810.