Table 5. . Gene polymorphisms with relevant clinical impact in human tumors which may also influence second-line drugs response and toxicity in high-grade osteosarcoma.

Genes	Polymorphism	Main findings associated with polymorphisms	Ref.
ABCB1	-3435C>T_rs1045642 -2677G>T/A_rs2032582	Possible associations with gastrointestinal, hematological toxicity or neurotoxicity after treatment with taxanes	[99]
ABCC1ABCC2	IVS11 -48C>T rs3765129 -24C>T rs717620	Associations with neutropenia in 85 advanced colorectal cancer patients treated with irinotecan as single agent	[100]
ABCC4	G>T rs9561778	Associations of T allele with hematological and gastrointestinal toxicity in 256 Bangladeshi breast cancer patients treated with cyclophosphamide, epirubicin and 5-fluorouracil Associations of T allele with leukopenia/neutropenia and gastrointestinal toxicity in a total of 403 Japanese breast cancer patients treated with cyclophosphamide-based combination therapy	[74] [101]
CYP2C8CYP3A5	*3 rs11572080 + rs10509681 *3 rs776746	CYP2C8*3 and CYP3A5*3 polymorphisms have been described as potentially predictive for hematological toxicity and neurotoxicity after taxanes treatment	[99]
UGT1A1	*28 rs8175347	Patients homozygous for the UGT1A1*28 allele have increased risk to develop hematological and/or digestive toxicities after irinotecan therapy	[102]
UGT1A1	*93 rs1092302	Association with neutropenia in 85 advanced colorectal cancer patients treated with irinotecan as single-agent	[100]
ERCC2 (XPD) and GSTT1	rs13181 and GSTT1 null	Associations between both polymorphisms and bleomycin-induced DNA damage	[103]