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Folate related gene polymorphisms and susceptibility to develop childhood acute lymphoblastic leukaemia

Ilan J N Koppen1, Frederik J R Hermans, Gertjan J L Kaspers

  • 1Department of Paediatric Oncology/Haematology, VU University Medical Center, Amsterdam, The Netherlands.

British Journal of Haematology
|September 25, 2009
PubMed

Insights

Genetic variations in folate metabolism may affect childhood acute lymphoblastic leukaemia (ALL) risk. Certain MTHFR gene polymorphisms appear to decrease ALL susceptibility in non-Asian populations.

Area of Science:

  • Genetics
  • Oncology
  • Epidemiology

Background:

  • Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer.
  • Genetic factors, including folate-related gene polymorphisms, may influence ALL susceptibility.

Purpose of the Study:

  • To review and synthesize findings from studies investigating the association between folate-related gene polymorphisms and ALL susceptibility.
  • To identify specific polymorphisms and populations where associations are most evident.

Main Methods:

  • Systematic review of 14 quality-assessed studies.
  • Analysis of data from 729 children and 1821 non-age-defined patients.
  • Comparison of results across different ethnic populations (Asian vs. European).

Main Results:

  • Polymorphisms in the MTHFR gene (677C>T and 1298A>C) may be associated with decreased ALL susceptibility in non-Asian populations.
  • Associations with other folate-related genes (MTRR, MTR, TYMS, SLC19A1, NNMT, SHMT1) were less clear and supported by limited studies.
  • Study results sometimes contradicted, potentially due to population differences.

Conclusions:

  • Constitutional differences in folate gene polymorphisms partly explain susceptibility to childhood ALL.
  • Further research is needed to clarify the role of various folate gene polymorphisms in ALL susceptibility, especially in diverse populations.

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