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Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia.
Cancer Epidemiol Biomarkers Prev. 2015 Jan; 24(1):48-56.CE

Abstract

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.

IMPACT

Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.

Authors+Show Affiliations

Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Liz.Milne@telethonkids.org.au.Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.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.Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.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.Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.School of Exercise and Health Sciences, Edith Cowan University, Mount Lawley, Western Australia, Australia.Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.Oncology Unit, The Children's Hospital at Westmead, Sydney, Australia.Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.Department of Clinical Biochemistry, Royal Perth Hospital and the School of Surgery, University of Western Australia, Perth, Western Australia, Australia.Sax Institute, Haymarket, New South Wales, Australia. Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25395472

Citation

Milne, Elizabeth, et al. "Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 24, no. 1, 2015, pp. 48-56.
Milne E, Greenop KR, Scott RJ, et al. Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia. Cancer Epidemiol Biomarkers Prev. 2015;24(1):48-56.
Milne, E., Greenop, K. R., Scott, R. J., Haber, M., Norris, M. D., Attia, J., Jamieson, S. E., Miller, M., Bower, C., Bailey, H. D., Dawson, S., McCowage, G. B., de Klerk, N. H., van Bockxmeer, F. M., & Armstrong, B. K. (2015). Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 24(1), 48-56. https://doi.org/10.1158/1055-9965.EPI-14-0680
Milne E, et al. Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia. Cancer Epidemiol Biomarkers Prev. 2015;24(1):48-56. PubMed PMID: 25395472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia. AU - Milne,Elizabeth, AU - Greenop,Kathryn R, AU - Scott,Rodney J, AU - Haber,Michelle, AU - Norris,Murray D, AU - Attia,John, AU - Jamieson,Sarra E, AU - Miller,Margaret, AU - Bower,Carol, AU - Bailey,Helen D, AU - Dawson,Somer, AU - McCowage,Geoffrey B, AU - de Klerk,Nicholas H, AU - van Bockxmeer,Frank M, AU - Armstrong,Bruce K, Y1 - 2014/11/13/ PY - 2014/11/15/entrez PY - 2014/11/15/pubmed PY - 2015/9/19/medline SP - 48 EP - 56 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol Biomarkers Prev VL - 24 IS - 1 N2 - 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. IMPACT: Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results. SN - 1538-7755 UR - https://www.unboundmedicine.com/medline/citation/25395472/Folate_pathway_gene_polymorphisms_maternal_folic_acid_use_and_risk_of_childhood_acute_lymphoblastic_leukemia_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25395472 DB - PRIME DP - Unbound Medicine ER -