Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia

Elizabeth Milne, Kathryn Greenop, R.J. Scott, M. Haber, M.D. Norris, J.R. Attia, Sarra Jamieson, M.R. Miller, Carol Bower, Helen Bailey, S. Dawson, G.B. Mccowage, Nicholas De Klerk, Frank Van Bockxmeer, B.K. Armstrong

Research output: Contribution to journalArticle

9 Citations (Scopus)
147 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)48-56
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 2015

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Folic Acid
Mothers
Genes
Confidence Intervals
Genotype
Fathers
Case-Control Studies
Parents
Logistic Models
Pediatrics
Pregnancy
Population

Cite this

Milne, Elizabeth ; Greenop, Kathryn ; Scott, R.J. ; Haber, M. ; Norris, M.D. ; Attia, J.R. ; Jamieson, Sarra ; Miller, M.R. ; Bower, Carol ; Bailey, Helen ; Dawson, S. ; Mccowage, G.B. ; De Klerk, Nicholas ; Van Bockxmeer, Frank ; Armstrong, B.K. / Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia. In: Cancer Epidemiology Biomarkers and Prevention. 2015 ; Vol. 24, No. 1. pp. 48-56.
@article{90ce2a7ab69940e9964fe0a88d2faf63,
title = "Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia",
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.",
author = "Elizabeth Milne and Kathryn Greenop and R.J. Scott and M. Haber and M.D. Norris and J.R. Attia and Sarra Jamieson and M.R. Miller and Carol Bower and Helen Bailey and S. Dawson and G.B. Mccowage and {De Klerk}, Nicholas and {Van Bockxmeer}, Frank and B.K. Armstrong",
year = "2015",
month = "1",
doi = "10.1158/1055-9965.EPI-14-0680",
language = "English",
volume = "24",
pages = "48--56",
journal = "Cancer Epidemiology, Biomarkers & Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research (AACR)",
number = "1",

}

Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia. / Milne, Elizabeth; Greenop, Kathryn; Scott, R.J.; Haber, M.; Norris, M.D.; Attia, J.R.; Jamieson, Sarra; Miller, M.R.; Bower, Carol; Bailey, Helen; Dawson, S.; Mccowage, G.B.; De Klerk, Nicholas; Van Bockxmeer, Frank; Armstrong, B.K.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 24, No. 1, 01.2015, p. 48-56.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia

AU - Milne, Elizabeth

AU - Greenop, Kathryn

AU - Scott, R.J.

AU - Haber, M.

AU - Norris, M.D.

AU - Attia, J.R.

AU - Jamieson, Sarra

AU - Miller, M.R.

AU - Bower, Carol

AU - Bailey, Helen

AU - Dawson, S.

AU - Mccowage, G.B.

AU - De Klerk, Nicholas

AU - Van Bockxmeer, Frank

AU - Armstrong, B.K.

PY - 2015/1

Y1 - 2015/1

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.

AB - 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.

U2 - 10.1158/1055-9965.EPI-14-0680

DO - 10.1158/1055-9965.EPI-14-0680

M3 - Article

VL - 24

SP - 48

EP - 56

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 1

ER -