TABLE 3.
The influence of MTHFD1, MTHFR, and TYMS polymorphisms on high-dose methotrexate-related toxicity in pediatric patients with non-Hodgkin lymphoma (n = 28)
| Polymorphism | Genotype | Number (%) | Anaemia grade ≥ 2a | Leucopoenia grade ≥ 2 | Thrombocytopenia grade ≥ 2 | Hepatotoxicity grade ≥ 1b | Mucositis grade ≥ 1 | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||||
| OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P | |||
| MTHFD1 1958G>A | GG | 11 (37.9) | Reference | 0.923 | Reference | 0.263 | Reference | 0.592 | Reference | 0.496 | Reference | 0.406 |
| GA | 16 (55.2) | 0.94 | 3.75 | 1.67 | 0.51 | 2.18 | ||||||
| AA | 2 (6.9) | (0.13-6.78) | (0.37–37.95) | (0.26–10.79) | (0.08–3.49) | (0.35–13.76) | ||||||
| MTHFR 677C>T | CC | 16 (55.2) | Reference | 0.164 | Reference | 0.006c | Reference | 0.041 | Reference | 0.087 | Reference | 0.901 |
| CT | 11 (37.9) | 5.33 | 1.86 | 11.14 | 0.13 | 1.11 | ||||||
| TT | 2 (6.9) | (0.51–56.24) | (1.12–3.07) | (1.11–112.01) | (0.01–1.34) | (0.21–5.80) | ||||||
| MTHFR 1298A>C | AA | 12 (41.4) | Reference | 0.908 | Reference | 0.158 | Reference | 0.069 | Reference | 0.968 | Reference | 0.824 |
| AC | 15 (51.7) | 1.13 | 0.25 | 0.17 | 0.96 | 1.21 | ||||||
| CC | 2 (6.9) | (0.15–8.21) | (0.04–1.71) | (0.03–1.14) | (0.16–5.80) | (0.22–6.61) | ||||||
| TYMS 2R>3R | 2R/2R | 7 (24.1) | Reference | 0.700 | Reference | 0.563 | Reference | 0.246 | Reference | 0.858 | Reference | 0.379 |
| 2R/3R | 12 (41.4) | 1.60 | 2.00 | 0.33 | 1.20 | 0.44 | ||||||
| 3R/3R | 10 (34.5) | (0.15–17.41) | (0.19–20.90) | (0.05–2.13) | (0.16–8.80) | (0.07–2.71) | ||||||
| TYMS 2R>3RC/3RGd | Low | 14 (48.3) | Reference | 0.815 | Reference | 0.262 | Reference | 0.284 | Reference | 0.455 | Reference | 0.284 |
| High | 13 (46.8) | 0.82 | 3.00 | 0.36 | 0.50 | 0.36 | ||||||
| (0.11–5.99) | (0.44–20.44) | (0.06–2.34) | (0.08–3.08) | (0.06–2.34) | ||||||||
CI = confidence interval; OR = odds ratio
TYMS low expression genotypes: 2RG/2RG, 2RG/3RC, and 3RC/3RC. TYMS high expression genotypes: 2RG/3RG, 3RC/3RG, and 3RG/3RG.
ORs, 95% CIs, and P values were calculated by univariable logistic regression and the dominant genetic model was used. Bold characters indicate statistically significant results
a
Data on anaemia missing for 1 patients (3.9%);
b
Data on hepatotoxicity missing for 4 patients (13.8%);
c
P-value was calculated using Fisher’s exact test;
d
Genotyping data missing for 2 patients (6.7%)