Table 3. The study of MTHFR polymorphisms and MTX therapy outcome for osteosarcoma patients.

Treatment regimes	Patient population	Race/ethnicity	MTHFR polymorphisms	Main results	Citations
MAP or VAC	Children and adolescents (n = 34)	Caucasian origin	C677T, A1298C	Patients with G3/G4 hematologic toxicity were more frequently TT than CT/CC for C677T/MTHFR (P = 0.023).	[31]
MAP	Patients aged >16 yrs (n = 58)	Caucasian origin	C677T, A1298C, C1305T	Methotrexate toxicity was increased in variants of MTHFR c. 1298A>C (P = 0.03).	[11]
APMI or APMIE	Adolescents and adults (n = 62)	Caucasian origin	C677T, A1298C	The MTHFR 677C allele was associated with higher degree of liver toxicity (88%, P = 0.007).	[30]
APMI	Adolescents and adults (n = 59)	Han nationality from mainland of China	C677T, A1298C	Patients with mutation of C677T were associated with higher degree of liver toxicity (P = 0.043) and fever reaction of MTX (P = 0.050) while G3/G4 hematologic toxicity were more likely to be noticed with TT than CT/CC (P = 0.095).	Present study