Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.
BACKGROUND
The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+).


METHODS
This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression.


RESULTS
There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-).


CONCLUSIONS
Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.
Spector
Logan G
LG
Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. spector@epi.umn.edu
Xie
Yang
Y
Robison
Leslie L
LL
Heerema
Nyla A
NA
Hilden
Joanne M
JM
Lange
Beverly
B
Felix
Carolyn A
CA
Davies
Stella M
SM
Slavin
Joanne
J
Potter
John D
JD
Blair
Cindy K
CK
Reaman
Gregory H
GH
Ross
Julie A
JA
D000208:Acute Disease; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002675:Child, Preschool; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005638:Fruit; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008431:Maternal-Fetal Exchange; D016017:Odds Ratio; D011247:Pregnancy; D059005:Topoisomerase II Inhibitors; D014675:Vegetables
D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors