MTHFR Gene Polymorphisms and Cancer Risk in Children and Adolescents: A Systematic Review and Meta-Analysis.

Background/

Objectives

MTHFR gene polymorphisms (677C>T and 1298A>C) correlate with various types of cancer across all age groups; however, a small number of studies have included solely children and adolescents. The aim of this systematic review and meta-analysis was to present and synthesize all the available evidence on the association between MTHFR gene polymorphisms and the incidence of all types of cancer in children and adolescences.

Methods

After a systematic search of all of the available data, original case-control studies involving children or adolescents with a confirmed diagnosis of any type of cancer and a molecular genetic test of MTHFR gene polymorphisms were included.

Results

A total of 53 original studies in children and adolescents with cancer were included in the systematic review. Among these, 40 studies reviewed children and adolescents with Acute Lymphoblastic Leukemia (ALL), 4 those with Acute Myeloblastic Leukemia (AML), 8 those with central nervous system (CNS) tumors and 3 those with other types of cancer. Children and adolescents with ALL had less frequent T allele sequences (CT and TT variations) of the 677C>T polymorphism compared to a healthy population (OR: 0.85; CI: 0.80-0.91; p < 0.00001). Concerning the 1298A>C polymorphism, the C allele sequences (AC and CC) did not present a statistically significant difference in frequency compared to a healthy population (OR: 1.01; CI: 0.95-1.08; p = 0.69).

Conclusions

Children and adolescents with ALL appeared to have the T allele sequences of the 677C>T polymorphism of the MTHFR gene less frequently compared to a healthy population.