Genetic variation in the folate metabolic pathway and risk of childhood leukemia

Lightfoot, Tracy; Johnston, W. Thomas; Painter, Dan; Simpson, Jill; Roman, Eve; Skibola, Chris F.; Smith, Martyn T.; Allan, James M.; Taylor, G. Malcolm

doi:10.1182/blood-2009-10-249722

Cited by 81 publications

(71 citation statements)

References 45 publications

(80 reference statements)

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“…Only three previous studies have investigated maternal folate pathway genotype in relation to ALL risk; two found that the child's genotype was more closely associated with risk than the mother's (19,35), while Lupo and colleagues found more associations with the mother's than the child's genotype (17). In our study, the findings for the child's genotype were generally consistent with those for maternal genotype.…”

Section: Discussionsupporting

confidence: 80%

“…The UKCCS reported null associations with MTHFR 677C>T and 1298A>C for both Band T-cell ALL (19), while Tong and colleagues reported evidence of a protective association between MTHFR 677TT genotype and both ALL subtypes (52). We found no evidence of associations between either SNP and B-cell ALL, and only weak evidence that the MTHFR 677TT genotype was associated with an elevated risk of T-cell ALL.…”

Section: Discussioncontrasting

confidence: 51%

“…Only the UK Childhood Cancer Study reported elevated ORs: 1.24 (95% CI, 1.00-1.53) and 1.88 (95% CI, 1.16-3.07) for the AG and GG genotypes, respectively (19). Vijayakrishnan and Houlston (13) reported a null result in their meta-analysis of four studies (18,(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

“…[16][17][18][19][20][21][22][23], 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR; refs. 17,22,[24][25][26][27][28], methylenetetrahydrofolate dehydrogenase (MTHFD1; refs.…”

Section: Introductionmentioning

confidence: 99%

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Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia

Milne

Greenop

Scott

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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)(2004)(2005)(2006)(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 vari-

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Section: Discussionsupporting

confidence: 80%

Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia

Milne

Greenop

Scott

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Further analysis stratified by cancer type showed 1420T allele was associated with a minor decreased risk only in leukemia, suggesting 1420T allele might be a protective factor for leukemia. It should be noted that the four relative small studies (Skibola et al, 2002;de Jonge et al, 2009;Lightfoot et al, 2010;Yang et al, 2011) with only 1572 cases and 1739 controls had driven the borderline inverse association, which may be due to selection bias. In stratifying analysis by source of control, the association between 1420T allele and reduced risk of cancer was significant in HB subgroup but not in PB subgroup.…”

Section: Discussionmentioning

confidence: 99%

C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysis

Zhong

Zhang²,

Hu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420T polymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a more precise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 available studies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significant association between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer, gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associated with decreased risk in leukemia . In summary, the findings suggest that SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decrease cancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis.

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Family‐based exome‐wide assessment of maternal genetic effects on susceptibility to childhood B‐cell acute lymphoblastic leukemia in hispanics

Archer¹,

Pérez-Andreu

Scheurer

et al. 2016

Cancer

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Background Children of Hispanic ancestry have a higher incidence of acute lymphoblastic leukemia (ALL) than other ethnic groups, but the genetic basis for racial disparities remain incompletely understood. Genome-wide association studies (GWAS) of childhood ALL to date have focused on inherited genetic effects; however, maternal genetic effects (the role of maternal genotype on offspring phenotype development) may also play a role in ALL susceptibility. Methods We conducted a family-based exome-wide association study (EXWAS) of maternal genetic effects among Hispanics with childhood B-cell ALL (B-ALL) using the Illumina Human Exome BeadChip. We used a discovery cohort of 312 Guatemalan and Hispanic American families and an independent replication cohort of 152 Hispanic American families. Results Three maternal SNPs approached our threshold for significance, after correction for multiple testing (P<1.0×10−6): MTL5 rs12365708 (RR=2.62, 95% CI=1.61-4.27, P=1.8×10−5); ALKBH1 rs6494 (RR=3.77, 95% CI=1.84-7.74, P=3.7×10−5); NEUROG3 rs4536103 (RR=1.75, 95% CI=1.30-2.37, P=1.2×10−4). While effect sizes were similar, these SNPs were not nominally significant in our replication cohort. In a meta-analysis comprised of the discovery cohort and the replication cohort, these SNPs were still not statistically significant after correction for multiple comparisons (rs12365708: pooled RR=2.27, 95% CI=1.48-3.50, P=1.99×10−4; rs6494: pooled RR=2.31, 95% CI=1.38-3.85, P=0.001; rs4536103: pooled RR=1.67, 95% CI=1.29-2.16, P=9.23×10−5). Conclusions In the first family-based EXWAS to investigate maternal genotype effects associated with childhood ALL, our results did not implicate a strong role of maternal genotype on disease risk among Hispanics; however, we identified three maternal SNPs that may play a modest role in susceptibility.

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Genetic variation in the folate metabolic pathway and risk of childhood leukemia

Cited by 81 publications

References 45 publications

Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia

Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia

C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysis

Family‐based exome‐wide assessment of maternal genetic effects on susceptibility to childhood B‐cell acute lymphoblastic leukemia in hispanics

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