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.