| Title: |
Maternal Red Blood Cell Folate and Infant Vitamin B 12 Status Influence Methylation of Genes Associated with Childhood Acute Lymphoblastic Leukemia |
| Authors: |
Potter, Catherine; Moorman, Anthony Vincent; Relton, Caroline Laura; Ford, Dianne; Mathers, John Cummings; Strathdee, Gordon; MKay, Jill Ann |
| Contributors: |
North of England Children's Cancer Research Fund (NECCR); Newcastle upon Tyne Hospitals Special Trustees NHS Foundation Trust |
| Source: |
Molecular Nutrition & Food Research ; volume 62, issue 22 ; ISSN 1613-4125 1613-4133 |
| Publisher Information: |
Wiley |
| Publication Year: |
2018 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Scope Inadequate maternal folate intake is associated with increased childhood acute lymphoblastic leukemia (ALL) risk. Folate provides methyl groups for DNA methylation, which is dramatically disrupted in ALL. Whether or not maternal folate (and related B‐vitamin) intake during pregnancy may affect ALL risk via influencing DNA methylation is investigated. Methods and Results Genes in which methylation changes are reported both in response to folate status and in ALL are investigated. Folate‐responsive genes ( n = 526) are identified from mouse models of maternal folate depletion during pregnancy. Using published data, 2621 genes with persistently altered methylation in ALL are identified. Overall 25 overlapping genes are found, with the same directional methylation change in response to folate depletion and in ALL. Hypermethylation of a subset of genes ( ASCL2, KCNA1, SH3GL3, SRD5A2 ) in ALL is confirmed by measuring 20 patient samples using pyrosequencing. In a nested cohort of cord blood samples ( n = 148), SH3GL3 methylation is inversely related to maternal RBC folate concentrations ( p = 0.008). Furthermore, ASCL2 methylation is inversely related to infant vitamin B12 levels. ( p = 0.016). Conclusion Findings demonstrate proof of concept for a plausible mechanism, i.e., variation in DNA methylation, by which low intake of folate, and related B‐vitamins during pregnancy may influence ALL risk. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/mnfr.201800411 |
| Availability: |
https://doi.org/10.1002/mnfr.201800411; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fmnfr.201800411; https://onlinelibrary.wiley.com/doi/pdf/10.1002/mnfr.201800411 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.427B08CF |
| Database: |
BASE |