Acute lymphoblastic leukaemia (ALL) is the most common paediatric
cancer, accounting for nearly 30% of all paediatric
cancers and 80% of childhood leukaemias. Polymorphisms in
folate-related genes may influence the susceptibility to
childhood ALL. This review summarizes the results of 14 studies that focussed on the relationship between
folate-related gene polymorphisms and the susceptibility to ALL and that fulfilled certain quality criteria. The total group consisted of 729 children and 1821 adults or non age-defined patients. The results of different studies sometimes contradict each other, for which there are several possible explanations. This includes an influence of the type of population studied, because there was a difference between Asian and European study results. Based on several studies, it is plausible that polymorphisms in the MTHFR gene, 677C>T and 1298A>C, are associated with a decreased susceptibility to
childhood ALL in non-Asian populations. Polymorphisms in other
folate related genes (MTRR, MTR [MS], TYMS [TS], SLC19A1 [RFC1],
NNMT, and SHMT1) are less clearly associated with susceptibility to ALL, and the number of included studies on this subject in this review is limited. Further investigations on the relevance of these polymorphisms need to be performed. In general, it is clear that susceptibility to (
childhood) ALL is partly related to constitutional differences in
folate gene polymorphisms.