Methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and risk of pediatric non-Hodgkin lymphoma in a German study population

Skibola and colleagues recently reported on a comprehensive evaluation of associations between polymorphisms in folate-metabolizing genes and adult non-Hodgkin lymphoma (NHL) risk in a large population-based case-control study conducted in the San Francisco Bay Area.¹  In contrast to most previous findings,^2-5  upon stratification by NHL histologic subtype, heterozygous or homozygous presence of the MTHFR 677T allele was associated with an 1.8-fold increased risk (adjusted for MTHFR 1298A>C) of follicular lymphoma. The authors suggested that low folate and elevated homocysteine levels may increase follicular lymphoma risk through increased DNAhypomethylation with potential consequences contributing to lymphoma risk (eg, chromosomal instability, reactivation of transposable elements).

Here, we report on the association of MTHFR 677 genotype with pediatric NHL analyzing 487 patients up to 18 years of age from the Austrian-German-Swiss multicenter trial NHL-BFM 95 conducted by the Berlin-Frankfurt-Münster (BFM) study group and 379 healthy controls. Patients were enrolled between April 1996 and March 2001. With regard to clinical characteristics of the investigated 487 NHL patients, 343 patients (70.4%) were of male sex and 222 (45.6%) were 10 years or older at the time of diagnosis. The distribution of the major histologic subtypes is shown in Table 1. Table 1 also summarizes the association of MTHFR 677 genotype with pediatric NHL in the entire patient group and in the major histologic subgroups. In the analysis, an increased risk of lymphoblastic lymphoma for individuals with the 677T>T genotype was observed (odds ratio = 2.14; 95% CI = 1.11-4.12; P = .02), while no significant associations were obtained for the entire patient group or other histologic subtypes.

Our findings do not support a general major influence of the MTFHR 677C>T polymorphism on the susceptibility to pediatric NHL in the investigated population. However, in accordance with the observation of Skibola et al in adult NHL,¹  our results suggest that folate metabolism may be associated with specific subtypes of pediatric NHL.