3.3 Influence of MTHFR C677T/A1298C on the survival of pediatric NHL
The median follow-up time was 37 months (range, 1–73 months) for the subgroup of genotyped patients (n = 158). K-M analysis comparing EFS for the C677T genotypes showed significant differences (P = 0.048; Fig. 1A.). The estimated 5-year EFS rate for patients with the CC, CT, and TT genotype was 68.0%, 87.7%, and 78.6%, respectively. Pairwise comparisons suggested that there was a significant difference only between the CC and CT genotypes (P = 0.013). When the whole subgroup of NHL cases with C677T sequencing was stratified into wild-type and mutant (677T carrier) groups, K-M analysis showed that 677T carriers had a better estimated 5-year EFS rate than those with the wild-type genotype (85.9% vs. 68.0%; P = 0.020; Fig. 1B.). Although no significant difference in OS was found between patients with C677T genotypes (P = 0.495 or P = 0.312; Figs. 1C and 1D), similar to EFS, 677T carriers also had a slightly better 5-year OS rate than those with the wild-type genotype (89.8% vs. 82.4%; P = 0.312; Fig. 1D). The A1298C polymorphism did not influence the survival of pediatric patients with NHL (Fig. S2A–D). Patients with different genotypes had similar 5-year EFS and OS rate.
Considering that BL and DLBCL are mature B cell NHL, which have the same criteria for risk stratification and treatment regimens but which differ from LBL and ALCL, the NHL subtype might be a confounding factor in analyzing the influence of MTHFR on the whole group of NHL. Accordingly, we performed K-M survival analysis in three subtype groups: BL/DLBCL (n = 81), LBL (n = 45), and ALCL (n = 32). The results indicate that patients with BL/DLBCL carrying the heterozygous C677T genotype had the highest rates for 5-year EFS (97.1%, Fig. 2A) and 5-year OS (100%, Fig. 2C) and that T carriers were associated with better EFS and OS rates (Figs. 2B and 2D). However, no significant difference was found in EFS and OS among the A1298C genotypes (Fig. S3). Both the C677T and A1298C polymorphisms did not have any impact on the EFS and OS in patients with LBL and ALCL.