Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia.
BACKGROUND
Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007).


METHODS
All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed.


RESULTS
There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation.


CONCLUSIONS
Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation.


CONCLUSIONS
Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Liz.Milne@telethonkids.org.au.
Elizabeth
E
Milne
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
Kathryn R
KR
Greenop
Hunter Medical Research Institute, John Hunter Hospital, New Lambton, New South Wales, Australia. School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, New South Wales, Australia. Hunter Area Pathology Service, HNEHealth, Newcastle, New South Wales, Australia.
Rodney J
RJ
Scott
Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
Michelle
M
Haber
Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
Murray D
MD
Norris
Hunter Medical Research Institute, John Hunter Hospital, New Lambton, New South Wales, Australia. School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
John
J
Attia
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
Sarra E
SE
Jamieson
School of Exercise and Health Sciences, Edith Cowan University, Mount Lawley, Western Australia, Australia.
Margaret
M
Miller
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
Carol
C
Bower
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.
Helen D
HD
Bailey
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
Somer
S
Dawson
Oncology Unit, The Children's Hospital at Westmead, Sydney, Australia.
Geoffrey B
GB
McCowage
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
Nicholas H
NH
de Klerk
Department of Clinical Biochemistry, Royal Perth Hospital and the School of Surgery, University of Western Australia, Perth, Western Australia, Australia.
Frank M
FM
van Bockxmeer
Sax Institute, Haymarket, New South Wales, Australia. Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
Bruce K
BK
Armstrong
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019587:Dietary Supplements / Q000032:analysis; D005260:Female; D005492:Folic Acid / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000235:genetics; D011247:Pregnancy; D012307:Risk Factors
D005492:Folic Acid