Table 1.

Examples of clinical pharmacoethnic differences in chemotherapeutic susceptibilities, with implicated genes and important known functional variants shown

DrugClinical findingsGenes implicatedImportant variantsMechanismsEthnic differences of variants
5-fluorouracilHematologic toxicities more common in AA > CAU;DPYDDPYD*2A(a) DPD deficiency;(a) Frequency of DPD deficiency is 8% AA, 2.8% CAU, < 1% ASN;
Diarrhea, mucositis, and nausea/vomiting more common in CAU > AATYMSTSER*2, *3(b) three copies of TYMS enhancer region tandem repeat (TSER*3) result in greater TS expression (and decreased toxicity)(b) 67% of ASN are TSER*3-TSER*3 genotype, compared with 30–40% of CAU
DoxorubicinIncreased cardiotoxicity in AAPossibly CBR1, CBR3Possibly increased CBR1-CBR3 conversion of doxorubicin to more cardiotoxic doxorubicinol
CyclophosphamidePossible decreasedefficacy in AA compared with CAUCYP3A4, CYP3A5, CYP2B6Many potentialsDecreased conversion of cyclophosphamide to more active metabolitesMany found
VincristineNeurotoxicity more common in CAU compared with AACYP3A5Vincristine metabolism by CYP3A5CYP3A5 expression more prevalent in AA (70%) compared with CAU (20%)
EGFR inhibitorsIncreased antitumor efficacyEGFRMany potentialsEast Asians have more EGFR mutations and are more susceptible to EGFR inhibitors

NOTE: Individual references for the supporting evidence are cited within the text.

Abbreviations: AA, African American; CAU, Caucasian; ASN, Asian; EGFR, epidermal growth factor receptor.