Table 1 Summary of the most common enzymes/transport systems, the genes that code for them, metabolised drugs and expected therapy outcomes
Enzyme/ Transporter | Gene | Variant alleles | Drug molecule | Effect | Neoplasm | Reference |
|---|---|---|---|---|---|---|
Dihydropyramidine dehydrogenase | DPYD | DYPD*13, DPYD*8, DPYD*7, DPYD*12, DPYD*3, DYPD*4, DPYD*2A, DPYD*9A | Fluoropyramidines – 5-fluorouracil, capecitabine, tegafur | Efficacy/Resistance/Toxicity | colorectal carcinoma, breast cancer | [4] |
head-neck cancer | [5] | |||||
Thymidylate synthetase | TYMS | TSER*2, TSER*3 | 5-fluorouracil, capecitabine | Efficacy/Toxicity | colorectal, bladder, gastric carcinoma | [4] |
Methylene tetrahydrofolate reductase | MTHFR | 667 C > T, 1298A > C, | 5-fluorouracil, methotrexate | Efficacy/Toxicity | colorectal carcinoma, ovarian cancer, gastric cancer | [4] |
Thiopurine S-methyltransferase | TPMT | TPMT*2–24 (TPMT*1, TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C, TPMT*4) | azathioprine, mercaptopirune, thioguanine | Dosage/Toxicity/ADR | acute lymphatic leukemia | [4] |
ovarian cancer | [6] | |||||
breast cancer | [7] | |||||
Uridine diphosphate glucuronosyl transferase | UGT1A1 | UGT1A1*27, UGT1A1*28, UGT1A1*6 | irinotecan | Toxicity/ADR | colorectal carcinoma | [4] |
Glutathione S-transferases | GST | GSTM1, GSTP1 | platinum compounds - cyclofosfamide, carboplatin, doxorubicin, cisplatin, oxaliplatin | Efficacy/Toxicity/ADR | colorectal cancer | [5] |
bladder, head and neck, lung, ovarian and testicular cancer | [7] | |||||
Excision repair cross complementing group 1 | ERCC1 | 496 C > T, 8092 C > A, 19007 T > C | platinum containing anti-cancer drugs | Efficacy/Toxicity | non-small cell lung carcinoma, bladder cancer | [4] |
colorectal carcinoma | [8] | |||||
Excision repair cross complementing group 2 | ERCC2 | 965 G > A, 225 A > C | platinum containing anticancer drugs - oxaliplatin | Efficacy/Toxicity | colorectal cancer | |
ovarian cancer | [9] | |||||
non-small cell lung carcinoma | [10] | |||||
ATP binding cassettes | ABCB1, ABCC2, ABCG2 | 1236 C > T, 3435 C > T, 2677 G > T, 421 C > A, ABCC2*2 | irinotecan | Efficacy/Toxicity/Resistance | ovarian cancer | [10] |
X-ray cross complementing group 1 | XRCC1 | 1301 G > A | platinum anti-cancer drugs, 5-fluorouracil | Efficacy/Toxicity | colorectal, gastric and non-small cell lung carcinoma | [4] |
Cytochrome P450 2D6 | CYP2D6 | about 80 CYP2D6 variant alleles; most common ones - CYP2D6*4, CYP2D6*3, CYP2D6*5 and CYP2D6*6 | tamoxifen | Efficacy/Toxicity | breast cancer | [4] |