Table 2.
Minor Allele Frequency of GWAS significant variants associated with chemotherapeutic toxicity.
| Associated non-uniform variants by ancestry | MAF by Population (HapMap) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Drug (Class) | SNP | Toxicity | Study Population | Gene | Location (GRCh38.p7) | HCB | YRI | CEU | Reference |
| thiopurine (antimetabolite) | rs79206939 | myelosuppression | East Asian (Korea) | FTO | 16:53826140 | 2.8* | 0 | 0 | (52) |
| 5-FU/FOLFOX | rs16857540 | myelosuppression | European (Spain) | NLGN1 | 3:174182785 | 0 | 37.2 | 15.3 | (55) |
| cis/carboplatin | rs2838566 | hepatotoxicity | East Asian (China) | intergenic | 21:44468699 | 7.1 | 33 | 0 | (61) |
| paclitaxel + epi. (taxane) | rs9501929 | neuropathy | European (USA) | TUBB2A | 6:3157620 | 0 | 28.6 | 4.7 | (59) |
| epi/doxo (anthracyclin) | rs229774 | cardiotoxicity | diverse (Canada) | RARG | 14:83435125 | 0 | 11.1 | 6.6 | (64) |
| melphalan (alkylating) | rs1469167 | oral mucositis | European (USA) | ALDH1A1 | 9:72942091 | 0 | 31.4 | 2.7 | (72) |
| epirubicin (anthracyclin) | rs4149639 | myelosuppression | East Asian (Japan) | TNFRSF1A | 12:6332835 | 11.4 | 22 | 0 | (63) |
| docetaxel (taxane) | rs3747851 | myelosuppression | East Asian (Japan) | DAB2IP | 9:121758981 | 0 | 15.1 | 0.4 | (63) |
| docetaxel (taxane) | rs875858 | neuropathy | European (USA) | VAC14 | 16:70741552 | 0 | 0 | 7.5 | (58) |
| paclitaxel (taxane) | rs17348202 | neuropathy | European (USA) | EPHA4 | 2:221207458 | 0 | 17.7 | 5.8 | (60) |
| glucocorticoid | rs2229288 | osteonecrosis | diverse (USA) | ZFHX3 | 16:72794405 | 0 | 0 | 0.5 | (65) |
| mercaptopurine | rs116855232 | dose tolerance | diverse (USA) | NUDT15 | 13:48045719 | 9.5 | 0 | 0.2 | (67) |
| cisplatin | rs62283056 | ototoxicity | European (USA) | WFS1 | 4: 6274903 | 0.3 | 17.6 | 22.9 | (75) |
| melphalan (alkylating) | rs1426765 | oral mucositis | European (USA) | intergenic | 3:25976116 | 0 | 0.8 | 14.4 | (72) |
| melphalan (alkylating) | rs6804277 | oral mucositis | European (USA) | intergenic | 3:25977271 | 0 | 10 | 12 | (72) |
| melphalan (alkylating) | rs1940228 | oral mucositis | European (USA) | intergenic | 11:103004647 | 0 | 6.1 | 1.7 | (72) |
| melphalan (alkylating) | rs948695 | oral mucositis | European (USA) | intergenic | 11:102990584 | 0 | 32.2 | 1.7 | (72) |
| oxaliplatin (platinum) | rs10486003 | neuropathy | East Asian (Korea) | intergenic | 7:97600466 | 23.3 | 0 | 10.2 | (73) |
Abbreviations: SNP (single nucleotide polymorphism); MAF (minor allele frequency); HCB (Han Chinese in Beijing, China); YRI (Yorubans in Ibadan, Nigeria); CEU (CEPH collection Europeans in Utah, United States of America); PMID# (PubMed Identification number); 5-FU (fluorouracil); FOLFOX (folinic acid, fluorouracil, oxaliplatin combination); epi (epirubicin), doxo (doxorubicin).
*
Minor Allele Frequency as reported by ExAc (http://exac.broadinstitute.org/); note that HapMap MAF is absent, and a MAF of 5.1% was observed in the Korean cohort used in the cited study.