Comprehensive Cyp2d6 Genotyping In A Multiracial Population Shows Differences In Allele Frequencies Between Races

e11095 Background: CYP2D6 genotyping has been investigated to avoid suboptimal response to tamoxifen, and although current data do not support routine genotyping in postmenopausal women, there is a need for further evaluation in multiracial populations. As part of a clinical trial evaluating genotype-guided tamoxifen dosing, we comprehensively examined CYP2D6 allele frequencies in women of heterogeneous ethnicity taking tamoxifen. Methods: As part of a multi-institution prospective clinical trial (LCCC 0801), patients on tamoxifen ≥ 4 months and not on potent CYP2D6 inhibiting medications were genotyped for CYP2D6 using the CYP450 AmpliChip. Tamoxifen dose was increased in patients with any intermediate or poor metabolizing (IM or PM) alleles [but not in patients homozygous for extensive metabolizing (EM) alleles]. Here we report the allele frequency data. Results: 499 evaluable patients participated in the study: 82 (16%) African-Americans (AA), 391 (78%) non-Hispanic whites, 11 Asians (2%), 13 Hispanics (3%), 1 American Indian, and 1 Pacific Islander. Genotyping revealed 152 (31%) EM/EM, 6 (1%) EM/UM (ultra-rapid), 104 (21%) EM/IM, 115 (23%) EM/PM, 28 (6%) IM/IM, 50 (10%) IM/PM, 31 (6%) PM/PM, 2 UM/PM, 2 UM/IM and 9 (2%) unknown. Allele frequencies are shown in the table. Of the 27 variant alleles evaluated, all were present in our population except *7,* 8, *11,*15, *19, *20, *36, *40, and *10XN. The odds ratio of an AA patient having a reduced metabolism allele was 2.0 (95% CI, 1.4-2.9) times higher than for white patients. Conclusions: AA women have a higher prevalence of reduced metabolism CYP2D6 alleles. Although the clinical impact of variations in tamoxifen metabolism is uncertain, it is possible that previously unrecognized racial pharmacogenetic heterogeneity contributes to breast cancer outcome disparities. CYP2D6 allele frequencies. Allele frequencies *1, *2 (EM) *35 (EM) *3-6 (PM) *9 (IM) *10 (IM) *17 (IM) *29 (IM) *41 (IM) Other Total patients (n=499) 0.50 0.04 0.22 0.02 0.02 0.03 0.02 0.11 0.04 African American patients (n=82) 0.34 0 0.15 0.01 0.02 0.16 0.09 0.14 0.09 Non-African American patients (n=417) 0.53 0.04 0.24 0.03 0.02 0.01 0 0.11 0.02