Table 2.
Population-specific frequencies of clinically important variants in genes of the ABCC subfamily
| Variant | Type | Minor allele frequencies (in %) | Clinical association of the minor allele | Effect or statistic | References | Sample size | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| EUR | AFR | EAS | SAS | AMR | AJ | ||||||
| ABCC1 (MRP1) | |||||||||||
| rs45511401 | Missense (G671V) | 5.6 | 1.2 | < 0.1 | 1.6 | 1.7 | 3.3 | Increased risk of anthracycline-induced cardiotoxicity | OR = 3.6 | Wojnowski et al. (2005) | 42 |
| rs4148350 | Intron | 7.3 | 10.4 | 4.0 | N.A | 8.4 | 6.6 | Increased risk of anthracycline-induced cardiotoxicity | OR = 3.4 | Visscher et al. (2012) | 156 and 188 and 96 |
| Toxicity of induction chemotherapy (idarubicin plus cytarabine) in acute myeloid leukemia | OR = 5.3 for grade 3–4 hepatic toxicity | Megías-Vericat et al. (2017) | 225 | ||||||||
| rs246221 | Synonymous | 30.5 | 65.2 | 42.5 | 20.3 | 35.2 | 32.1 | Decreased risk of anthracycline-induced cardiotoxicity | Increased LVFS of homozygous carriers (40.7%) compared to het and controls (38.4%) | Semsei et al. (2012) | 164 |
| rs3743527 | 3′ UTR | 22.6 | 14.3 | 45.7 | N.A | 27.0 | 23.8 | Increased risk of anthracycline-induced cardiotoxicity | Decreased LVFS of homozygous carriers (34%) compared to het and controls (39.3%) | Semsei et al. (2012) | 168 |
| rs17501331 | Intron | 10.3 | 2.2 | 0 | N.A | 5.8 | 11.7 | Increased risk of irinotecan-induced neutropenia | β = − 0.295 | Li et al. (2018b) | 78 |
| rs212091 | 3′UTR | 14.9 | 13.0 | 25.4 | N.A | 10.2 | 9.7 | Virological failure of protease inhibitor regimens in HIV patients | OR = 4.4 | Coelho et al. (2013) | 87 |
| rs119774 | Intron | 6.8 | 1.6 | 0.3 | N.A | 4.4 | 6.9 | Increased response to montelukast in asthma | p = 0.004 when comparing hom vs het carriers | Lima et al. (2006) | 49 |
| rs2074087 | Intron | 84.4 | 81.5 | 82.5 | 68.2 | 78.9 | 77.0 | Increased risk of azathioprine-induced lymphopenia | OR = 3.4 | Lee et al. (2015) | 131 |
| ABCC2 (MRP2) | |||||||||||
| rs8187710 | Missense (C1515Y) | 5.6 | 15.7 | < 0.1 | 1.9 | 4.1 | 12.9 | Increased risk of anthracycline-induced cardiotoxicity | OR = 2.3 | Wojnowski et al. (2005) | 44 |
| rs3740065 | Intron | 9.7 | 21.6 | 34.1 | N.A | 14.0 | 17.2 | Response of patients with invasive breast cancer to tamoxifen monotherapy | HR = 10.6 | Kiyotani et al. (2010) | 282 |
| rs3740066 | Synonymous | 37 | 25.9 | 23 | 32.6 | 34.9 | 34.5 | Severe toxicity of irinotecan in NSCLC patients | OR = 5.6 | Han et al. (2009) | 107 |
| rs12762549 | Intergenic | 46.8 | 43.0 | 56.5 | N.A | 49.3 | 51.7 | Leukopenia risk upon docetaxel therapy | OR = 3.1 | Kiyotani et al. (2008) | 113 |
| Response of NSCLC patients to second line docetaxel therapy | OR = 7.3 | Szczyrek et al. (2017) | 52 | ||||||||
| rs717620 | 5′ UTR | 19.9 | 5.8 | 21.4 | 11.3 | 13.0 | 20.0 | Poor response and reduced OS of SCLC patients undergoing etoposide and/or platinum-based therapy | HR = 2.1 and 1.9 for response and OS, respectively | Campa et al. (2012) | 167 and 127 |
| rs17222723 | Missense (V1188E) | 5.6 | 6.0 | < 0.1 | 1.8 | 3.6 | 12.8 | Increased response of esophageal cancer patients to platinum-based therapy | OR = 0.21 of carriers compared to controls | Rumiato et al. (2016) | 116 |
| ABCC3 (MRP3, MOAT-D) | |||||||||||
| rs1051640 | Synonymous | 18.2 | 8.6 | 5.6 | 10.3 | 8.6 | 18.7 | Increased risk of cisplatin-induced hearing loss | OR = 1.8 | Pussegoda et al. (2013) | 247 |
| rs4148416 | Synonymous | 5.4 | 19.6 | 15.0 | 8.8 | 14.4 | 5.8 | Reduced OS of osteosarcoma patients after chemotherapy | HR = 8.1 per allele | Caronia et al. (2011) | 91 |
| Poor response to chemotherapy in osteosarcoma patients | OR = 3.8 | Yang et al. (2013) | 45 | ||||||||
| rs4148405 | Intron | 14 | 43.7 | 21.7 | N.A | 21.8 | 21 | Shorter disease-free survival in acute myeloid leukemia patients treated with cytarabine and etoposide | HR = 3.2 | Yee et al. (2013) | 153 |
| ABCC4 (MRP4, MOAT-B) | |||||||||||
| rs2274405 | Synonymous | 34.1 | 30.3 | 47.1 | 36.1 | 42.7 | 46.4 | Increased response of esophageal cancer patients to platinum-based therapy | OR = 0.56 and 0.15 of het and hom carriers, respectively, compared to controls | Rumiato et al. (2016) | 116 |
| ABCC5 (MRP5, MOAT-C) | |||||||||||
| rs3749438 | 3′ UTR | 36.1 | 26.2 | 40.6 | N.A | 28.4 | 39.7 | Increased risk of irinotecan-induced severe toxicity in metastatic colorectal cancer patients | OR = 1.9–2.1 | Chen et al. (2015a) | 452 and 322 |
| rs10937158 | Intron | 54.4 | 74.7 | 86.0 | N.A | 51.0 | 53.3 | Decreased risk of irinotecan-induced severe toxicity in metastatic colorectal cancer patients | OR = 0.4–0.45 | Chen et al. (2015a) | 328 and 448 |
| rs7627754 | Promoter | 11.4 | 36.0 | 34.9 | N.A | 18.5 | 7.6 | Increased risk of doxorubicin-induced cardiotoxicity | 8–12% reduction of ejection and shortening fractions of hom carriers | Krajinovic et al. (2016) | 251 |
| rs7636910 | Synonymous | 36.9 | 26.8 | 41.5 | 36.4 | 26.9 | 40.9 | Increased response and OS in pancreatic adenocarcinoma patients treated with gemcitabine-based chemoradiotherapy | OR = 1.7 | Tanaka et al. (2011) | 261 |
| ABCC6 (MRP6, MOAT-E) | |||||||||||
| rs2238472 | Missense (R1268Q) | 28.2 | 10.1 | 12.3 | 18.2 | 31.3 | 17.0 | Increased toxicity of docetaxel and thalidomide in castration-resistant prostate cancer patients | p = 0.006 | Deeken et al. (2009) | 47 |
| ABCC10 (MRP7) | |||||||||||
| rs2125739 | Missense (I948T) | 25.1 | 31.9 | 10.9 | 18.0 | 18.7 | 21.3 | Associated with nausea of paclitaxel and carboplatin therapy in ovarian cancer patients in exploratory analysis | p = 0.002 | Bergmann et al. (2012) | 92 |
| Increased OS in CRC patients who received oxaliplatin- based chemotherapy | OR = 0.56 | Kap et al. (2016) | 623 | ||||||||
| ABCC11 (MRP8) | |||||||||||
| rs17822931 | Missense (G180R) | 13 | 2.8 | 87 | 40.6 | 16.2 | 10.8 | Reduced MRP8 expression and increased disease-free survival upon nucleoside-based chemotherapy | p < 0.03 | Guo et al. (2009) and Uemura et al. (2010) | / |
CRC colorectal cancer, OR odds ratio, LVFS left-ventricular fraction shortening, OS overall survival, NSCLC non-small cell lung cancer, EUR Europeans, AFR Africans, EAS East Asians, SAS South Asians, AMR Latinos, AJ Ashkenazi Jews, N.A. not available