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- W2324394239 abstract "Abstract #3089 Background: Cytochrome P450 2D6 (CYP2D6), a phase I drug metabolising enzyme, is involved in the metabolism of up to 25% of all drugs. The CYP2D6 gene is highly polymorphic with over 60 reported variant forms. Many of these have been classified by their effect on drug metaboliser status (poor, intermediate, extensive and ultra). Many variants have low minor allele frequencies (MAF) and metaboliser classification is not always certain. There is conflicting evidence for the potential predictive value of CYP2D6 genotype in patients treated with tamoxifen. In this study we investigate the association of the CYP2D6 gene variants with breast cancer survival in patients treated with tamoxifen. Methods: Invasive breast cancer cases (n=6510), came from SEARCH (East Anglian, UK population-based study), 3155 of these cases had received Tamoxifen therapy. CYP2D6 single nucleotide polymorphisms (SNPs) for genotyping were selected using 2 approaches: (i) Known CYP2D6 functional variants (n=13; MAF>0.01), (ii) tag SNPs , that efficiently tagged all known CYP2D6 common variants on the HapMap database (n=5; MAF>0.05), such that known common SNPs had an r p 2 of >0.8 with at least one tagSNP. (Pairwise correlation coefficient (r p 2 ) is a measure of how well one SNP tags another.) The combination of these two approaches aims to capture all known functional variants as well as any, as yet undiscovered variants that may be tagged by the common tagSNPs. Genotyping was carried out using Taqman Assays by Design. Results: Preliminary results, from this ongoing study, indicate that in patients treated with tamoxifen, one rare functional variant (carrier frequency = 0.02), CYP2D6*6, is associated with decreased breast cancer survival (P=0.007; HR=2.03; 95%CI=1.21-3.40), in comparison to patients who have not received hormone therapy (P=0.359; HR=0.52; 95%CI=0.13-2.10). None of the common tagSNPs (MAF>0.05) were associated with differences in survival (at P Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3089." @default.
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- W2324394239 date "2009-01-15" @default.
- W2324394239 modified "2023-09-27" @default.
- W2324394239 title "Cytochrome P450 2D6 variants and their association with breast cancer survival." @default.
- W2324394239 doi "https://doi.org/10.1158/0008-5472.sabcs-3089" @default.
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