Table 2.
Summary of SNP-drug relevant associations according to PharmGKB and drug labels
| Drug | Gene | SNP | Reference Genotype | Risk Genotype | CA Level: D, E, T, Pk | Drug label | Implications |
|---|---|---|---|---|---|---|---|
| Azathioprine | ITPA | rs7270101 | AA | AC, CC | 2B: T | T | Moderate risk of toxicity |
| Capecitabine | UMPS | rs1801019 | GG, CG | CC | 2B: T | A | Moderate risk of toxicity |
| Carboplatin | ERCC1 | rs11615 | GG | AA, AG | 2B: E, T | I | Moderate risk of inefficacy and toxicity |
| ERCC1 | rs3212986 | AA | AC, CC | 2B: T | Moderate risk of toxicity | ||
| GSTP1 | rs1695 | GG | AA, AG | 2A: T | Moderate risk of toxicity | ||
| MTHFR | rs1801133 | AA | AG, GG | 2A: E | Moderate risk of inefficacy | ||
| NQO1 | rs1800566 | GG | AA, AG | 2A: E | Moderate risk of inefficacy | ||
| XRCC1 | rs25487 | CC | CT, TT | 2B: E | Moderate risk of inefficacy | ||
| Cyclophosphamide | GSTP1 | rs1695 | AA, AG | GG | 2A: E, T | I | Moderate risk of inefficacy and toxicity |
| SOD2 | rs4880 | AA | AG, GG | 2B: E | Moderate risk of inefficacy | ||
| TP53 | rs1042522 | CC | CG, GG | 2B: E, T | Moderate risk of inefficacy and toxicity | ||
| Cisplatin | ERCC1 | rs11615 | GG | AA, AG | 2B: E, T | I | Moderate risk of inefficacy and toxicity |
| ERCC1 | rs3212986 | AA | AC, CC | 2B: T | Moderate risk of toxicity | ||
| GSTP1 | rs1695 | AA | AG,GG | 2B: T | Moderate risk of toxicity | ||
| NQO1 | rs1800566 | GG | AA, AG | 2A: E | Moderate risk of inefficacy | ||
| TP53 | rs1042522 | CC | CG, GG | 2B: E, T | Moderate risk of inefficacy and toxicity | ||
| XPC | rs2228001 | TT | GT, GG | 1B: T | High risk of toxicity | ||
| XRCC1 | rs25487 | CC | CT, TT | 2B: E | Moderate risk of inefficacy | ||
| Doxorubicin | NQO1 | rs1800566 | GG | AA, AG | 2A: E | I | Moderate risk of inefficacy |
| Etoposide | DYNC2H1 | rs716274 | AA | AG, GG | 2B: T | I | Moderate risk of toxicity |
| Fentanyl,Metadone, Morphine,Opioids, Oxycodone, Tramadol | ABCB1 | rs1045642 | AA, AG | GG | 2B: D, E | * | Moderate risk of inefficacy. Consider dose increase |
| Fluorouracil | GSTP1 | rs1695 | AG, GG | AA | 2A: E | A | Moderate risk of inefficacy |
| TP53 | rs1042522 | CC | CG, GG | 2B: E, T | Moderate risk of inefficacy and toxicity | ||
| UMPS | rs1801019 | GG, CG | CC | 2B: T | Moderate risk of toxicity | ||
| Irinotecan | C8ORF34 | rs1517114 | GG | CG, CC | 2B: T | A | Moderate risk of toxicity |
| SEMA3C | rs7779029 | TT | CT, CC | 2B: T | Moderate risk of toxicity | ||
| UGT1A1 | rs4148323 | GG | GA, AA | 2A | Moderate risk of toxicity | ||
| Methotrexate | ABCB1 | rs1045642 | GG | AG, AA | 2A: T | I | Moderate risk of toxicity |
| ATIC | rs4673993 | CC, TC | TT | 2B: E | Moderate risk of inefficacy | ||
| MTHFR | rs1801133 | GG | AA, AG | 2A: D, E, T | Consider dose reduction | ||
| MTRR | rs1801394 | AA | AG, GG | 2B: T | Moderate risk of toxicity | ||
| SLCO1B1 | rs11045879 | CC | CT, TT | 2A: T | Moderate risk of toxicity | ||
| Ondansetron | ABCB1 | rs1045642 | AA | AG, GG | 2A: E | I | Moderate risk of inefficacy |
| Oxaliplatin | ERCC1 | rs11615 | GG | AA, AG | 2B: E, T | I | Moderate risk of inefficacy and toxicity |
| ERCC1 | rs3212986 | AA | AC, CC | 2B: T | Moderate risk of toxicity | ||
| GSTP1 | rs1695 | GG | AA, AG | 2A: T | Moderate risk of toxicity | ||
| NQO1 | rs1800566 | GG | AA, AG | 2A: E | Moderate risk of inefficacy | ||
| XRCC1 | rs25487 | CC | CT, TT | 2B: E | Moderate risk of inefficacy | ||
| Paclitaxel | TP53 | rs1042522 | CC | CG, GG | 2B: E, T | I | Moderate risk of inefficacy and toxicity |
| Rituximab | FCGR3A | rs396991 | CC, AC | AA | 2B: E | T | Moderate risk of inefficacy |
| Tamoxifen | CYP2D6 | rs3892097 | CC, CT | TT | 2A: E | T | Moderate risk of inefficacy |
| CYP2D6 | rs3892097 | TT | CT, CC | 2A: T | Moderate risk of toxicity | ||
| Tegafur | DPYD | rs67376798 | TT | AA, AT | 1A: T, Pk | I | High risk of toxicity |
| UMPS | rs1801019 | GG, CG | CC | 2B: T | Moderate risk of toxicity | ||
| Trastuzumab | FCGR2A | rs1801274 | AA | AG, GG | 2B: E | T | Moderate risk of inefficacy |
| FCGR3A | rs396991 | CC | AC, AA | 2B: E | Moderate risk of inefficacy | ||
| Vincristine | CEP72 | rs924607 | CC, CT | TT | 2B: T | I | Moderate risk of toxicity |
*As this line describes a group of drugs, no information from a single drug label can be provided. This table lists the SNPs with levels of evidence 1 and 2 for the chemotherapeutic drugs and some others frequently employed in cancer patients (ondansetron and some pain relief drugs), that still have not a published guideline with therapeutic recommendations. The information about the “reference” and “risk” genotypes, with the proposed implications if the patient bears the risk one is provided. “CA” column describes the level of evidence and the way in which the risk genotype affects the drug mechanism (D, dosage; E, efficacy; Pk, pharmacokinetics; T, toxicity) and what does the drug label (FDA or EMA) state about performing genetic tests when prescribing that drug (T, testing required or recommended; A, actionable; I, informative), not specifying genes or variants. SNPs related with a set of drugs have not been listed, this table only includes the genes and SNPs directly linked with each individual drug. Date of PharmGKB access 15 January 2019. SNPs: single nucleotide polymorphisms; CA: clinical annotation