MTHFR rs1801133 polymorphism is associated with increased risk of B-cell precursor lymphoblastic leukaemia with recurrent genetic aberrations of fetal origin

Cancer Epidemiology
Alython Araujo Chung-Filhoon behalf the Brazilian Collaborative Study Group of Infant Acute Leukaemia (BCSGIAL)

Abstract

Childhood acute lymphoblastic leukaemia (ALL) is a heterogeneous disease associated with multiple risk factors including genetic susceptibility. Polymorphisms in folate genes have been associated with a protective effect against ALL, although some studies contradict these findings. We aimed to test whether there is an association between the MTHFR rs1801133 variant and the occurrence of B-cell precursor ALL (BCP-ALL) taking in account molecularly distinct subtypes of fetal origin. We performed a case-control genotyping study with 2067 samples, 1309 ALL and 758 controls, from children aged ≤ 15 years for MTHFR rs1801133 polymorphism. Risk associations were calculated by odds ratios estimated with unconditional logistic regression, adjusted for frequency-matched ethnic groups. Overall, MTHFR rs1801133 does not impact ALL risk in children with more than 6 years of age. A significant positive association for MTHFR rs1801133 variant was found for ALL with KMT2A-r in the dominant model (adj. OR, 1.48, 95 % CI, 1.01-2.17), while ETV6-RUNX1 and Hyperdiploid subgroups have shown a borderline effect (adj. OR, 1.33, 95 % CI, 0.99-1.78). The polymorphism MTHFR rs1801133 increased the risk of infant ALL in Brazilian population.

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