Table 4.
Relations between CYP2C19, CYP2D6, CYP3A5 and SULT1A1 genotypes and tamoxifen and its metabolites in postmenopausal women (n = 90)
| Median concentration [q1 - q3] 1 | ||||||||
|---|---|---|---|---|---|---|---|---|
| Genotype (n) | tamoxifen | 4OHtam | 4OHNDtam | NDtam | NDDtam | tamNox | ||
| CYP2C192 | *2/*2 | (4) | 107 [79 - 137] | 5.1 [3.3 - 5.2] | 45.7 [41.3 - 54.7] | 263 [156 - 404] | 47.0 [39.0 - 67.4] | 12.8 [10.3 - 31.8] |
| *1/*2 | (15) | 107 [79 - 140] | 5.8 [5.1 - 8.9] | 61.2 [43.2 - 83.9] | 233 [194 - 322] | 44.8 [40.2 - 71.4] | 9.7 [8.5 - 16.5] | |
| *1/*1 | (35) | 92 [79 - 118] | 5.5 [4.6 - 6.8] | 49.6 [44.7 - 61.6] | 231 [190 - 357] | 38.1 [26.7 - 46.4] | 9.5 [7.4 - 12.7] | |
| Vt*17 | (33) | 95 [76 - 126] | 6.1 [5.0 - 7.4] | 53.3 [41.4 - 67.4] | 229 [196 - 319] | 37.8 [25.6 - 55.1] | 9.1 [6.3 - 10.8] | |
| *17/*17 | (3) | 154 [31 - 157] | 11.3 [3.0 - 17.2] | 94.3 [34.0 - 184.8] | 341 [142 - 438] | 36.9 [15.7 - 79.0] | 11.1 [3.5 - 11.7] | |
| P3 | 0.371 | 0.240 | 0.652 | 0.600 | 0.022* | 0.002** | ||
| CYP2D64 | PM | (6) | 85 [58 - 125] | 4.0 [3.1 - 5.5] | 37.4 [31.8 - 48.2] | 296 [179 - 444] | 47.0 [22.8 - 55.9] | 9.2 [6.1 - 21.0] |
| IM | (32) | 87 [78 - 141] | 5.9 [4.6 - 6.9] | 50.5 [38.6 - 62.8] | 243 [217 - 358] | 38.2 [24.9 - 44.7] | 9.4 [7.1 - 11.0] | |
| Wt/Wt | (51) | 99 [80 - 124] | 6.1 [5.0 - 8.1] | 55.5 [45.7 - 69.7] | 223 [117 - 299] | 40.4 [33.0 - 55.6] | 9.8 [7.4 - 13.4] | |
| UM | (1) | 107 | 5.8 | 46.3 | 185 | 40.3 | 9.0 | |
| P | 0.358 | 0.019* | 0.009** | 0.044* | 0.413 | 0.958 | ||
| CYP3A5 | Vt/Vt | (76) | 96 [75 - 127] | 5.6 [4.7 - 7.0] | 49.9 [41.3 - 65.5] | 228 [189 - 316] | 38.4 [27.0 - 51.4] | 9.4 [6.9 - 11.8] |
| Wt/Vt | (14) | 102 [81 - 162] | 6.8 [5.7 - 10.2] | 54.6 [49.4 - 80.6] | 297 [221 - 396] | 45.7 [32.7 - 67.3] | 12.0 [9.7 - 14.5] | |
| P | 0.203 | 0.074 | 0.154 | 0.075 | 0.052 | 0.044* | ||
| SULT1A1 | Vt/Vt | (14) | 91 [68 - 138] | 5.5 [4.1 - 7.5] | 48.6 [40.4 - 60.7] | 228 [185 - 353] | 37.1 [23.4 - 49.8] | 9.3 [6.9 - 11.8] |
| Wt/Vt | (32) | 103 [90 - 141] | 6.0 [5.1 - 7.3] | 58.5 [46.2 - 75.3] | 244 [201 - 361] | 44.8 [37.9 - 57.6] | 10.7 [8.7 - 15.2] | |
| Wt/Wt | (44) | 87 [80 - 105] | 5.4 [4.6 - 8.9] | 51.3 [40.8 - 73.5] | 219 [183 - 294] | 36.9 [25.7 - 49.4] | 9.0 [6.8 - 10.1] | |
| P | 0.649 | 0.512 | 0.286 | 0.755 | 0.197 | 0.712 | ||
| SULT1A1copy numbers | 1 | (3) | 84 [80 - 168] | 6.7 [6.1 - 8.9] | 55.1 [49.0 - 85.0] | 278 [217 - 364] | 37.9 [24.2 - 60.4] | 9.7 [6.9 - 10.6] |
| 2 | (59) | 92 [68 - 123] | 5.6 [4.6 - 6.8] | 50.5 [41.2 - 64.4] | 227 [188 - 299] | 38.4 [27.7 - 47.9] | 9.4 [6.6 - 11.7] | |
| 3 | (21) | 107 [87 - 162] | 6.9 [5.2 - 9.8] | 52.7 [46.6 - 80.2] | 271 [198 - 395] | 46.5 [33.0 - 59.2] | 9.8 [8.3 - 13.8] | |
| 4 | (5) | 103 [82 - 139] | 5.1 [4.2 - 7.5] | 58.6 [39.1 - 71.7] | 223 [205 - 346] | 38.1 [28.4 - 62.3] | 12.7 [8.4 - 14.5] | |
| 5 | (2) | 86 [51 - 122] | 6.2 [4.1 - 8.4] | 49.2 [32.4 - 66.1] | 260 [150 - 371] | 45.1 [23.1 - 67.2] | 11.7 [5.6 - 17.7] | |
| P4 | 0.352 | 0.863 | 0.719 | 0.475 | 0.370 | 0.280 | ||
1Median concentration [quartile 1 - quartile 3] values of tamoxifen and metabolites are given as ng/ml.
2*2/*2, encodes defective CYP2C19 activity; Vt*17, subjects heterozygous for the variant type allele CYP2C19*17 (*1/*17 and *2/*17); *17/*17, encodes ultra rapid CYP2C19 activity.
3P values were calculated by multivariate logistic regression model, *p < 0.05. Adjusted for CYP2C19, CYP2D6, CYP3A5, SULT1A1, SULT1A1 copy number, FSH and SHBG.
4PM, poor metabolizer; IM, wild type/variant type; Wt/Wt, wild type/wild type; UM, ultra rapid metabolizer.