Table 2.
CYP2D6 genotyping and prevalence of CYP2D6 metabolism phenotype in BIG 1-98 trial participants*
| CYP2D6 allele† | Assessable, No. | Polymorphic alleles, No. (%) | Genotype, % |
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| SNP | Homozygous | Heterozygous | Wild-type | |||
| CYP2D6*4 | 1846G>A (rs2892097) | 3828 | 1444 (18.9) | 8.6 | 20.5 | 70.9 |
| CYP2D6*2, *4, *10, *41 | 4180G>C (rs1135840) | 0 | — | — | — | — |
| CYP2D6*10,*4 | 100C>T (rs1065852) | 0 | — | — | — | — |
| CYP2D6*41 | 2988G>A (rs28371725) | 3842 | 643 (8.4) | 4.2 | 8.4 | 87.4 |
| CYP2D6*3 | 2549delA (rs35742686) | 3012 | 80 (1.3) | 0.4 | 1.9 | 97.7 |
| CYP2D6*6 | 1707delT (rs5030655) | 2707 | 101 (1.9) | 0.2 | 3.3 | 96.5 |
| CYP2D6*7 | 2935A>C (rs5030867) | 2767 | 0 | 0.0 | 0.0 | 100.0 |
| CYP2D6*17 | 1023C>T (rs28371706) | 0 | — | — | — | — |
| 2850C>T (rs16947) | 2285 | 1550 (33.9) | 16.2 | 35.4 | 48.4 | |
| CYP2D6 metabolism phenotype‡, No. (%) | ||||||
| Patients classified | — | 4393 (100.0) | — | — | — | — |
| Poor metabolizer | — | 365 (8.3) | — | — | — | — |
| Intermediate metabolizer | — | 1294 (29.5) | — | — | — | — |
| Extensive metabolizer | — | 2734 (62.2) | — | — | — | — |
BIG = Breast International Group; CYP2D6 = Cytochrome P450 2D6; SNP = single-nucleotide polymorphism; — = not applicable.
CYP2D6*4 (1846G>A; rs2892097) and CYP2D6*41 (2988G>A; rs28371725) were genotyped in all 4861 patient DNA samples; other alleles were genotyped in 3691 patient DNA samples. One hundred seventy-nine patient DNA samples failed CYP2D6 genotyping. Genotyping was done using polymerase chain reaction–based methods.
Patients were categorized into predicted metabolism phenotypes as follows: poor metabolizer (PM) phenotypes were homozygous or compound heterozygous for CYP2D6*3, CYP2D6*4, CYP2D6*6 or CYP2D6*7 alleles (PM alleles); intermediate metabolizer (IM) phenotypes carried either homozygous CYP2D6*41 alleles (IM alleles) or a CYP2D6*41 allele in combination with a PM allele (ie, IM/IM or IM/PM alleles, respectively; n = 215 patients; 5%), or were heterozygous carriers of one PM or IM allele with an extensive metabolizer (EM) allele (heterozygous for EM allele or hetEM; n = 1079 patients; 24.5%); EM phenotypes were characterized by the absence of PM and IM alleles.