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Table 2 Results of unadjusted and adjusted Cox regression analysis for breast cancer specific survival in common (tagSNPs) and functional polymorphisms of CYP2D6

From: CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen

    No tamoxifen (unadjusted) All tamoxifen-treated patients (unadjusted) ER-positive patients treated with tamoxifen (unadjusted) ER-positive patients treated with tamoxifen (adjusted)
†SNP Metaboliser Status MAF** P-value Hazard ratio 95% CI** P-value Hazard ratio 95% CI** P-value Hazard ratio 95% CI** P-value Hazard ratio 95% CI**
CYP2D6 functional SNPs              
CYP2D6*41 (IM) 0.09 0.89 1.02 0.72-1.46 0.12 0.79 0.59-1.07 0.43 0.85 0.57-1.27 0.69 0.88 0.48-1.62
CYP2D6*4 (PM) 0.2 0.34 0.88 0.69-1.15 0.89 1.01 0.83-1.24 0.93 1.01 0.78-1.32 0.39 1.17 0.82-1.68
CYP2D6*5 (PM) 0.04 0.49 2.01 0.28-14.3 n/a n/a n/a n/a n/a n/a n/a n/a n/a
CYP2D6*6 (PM) 0.01 0.76 1.17 0.43-3.14 0.02 1.95 1.12-3.40 0.04 2.14 1.05-4.36 0.33 1.8 0.56-5.80
CYP2D6*9 (IM) 0.03 0.53 0.8 0.40-1.60 0.45 1.18 0.76-1.83 0.62 1.18 0.62-2.23 0.33 1.52 0.65-3.52
CYP2D6*10 (IM) 0.02 0.93 0.96 0.42-2.19 0.61 1.22 0.57-2.59 n/a n/a n/a n/a n/a n/a
CYP2D6*UM (UM) 0.08 0.65 1.57 0.22-11.3 0.45 0.47 0.07-3.34 n/a n/a n/a n/a n/a n/a
§CYP2D6*PM Model 1 (PM) ‡‡N/A 0.46 0.77 0.39-1.52 0.78 0.93 0.55-1.57 0.98 1.01 0.51-2.00 0.32 1.57 0.64-3.84
§§CYP2D6*PM Model 2 (PM) ‡‡N/A 0.85 0.97 0.72-1.31 0.63 1.06 0.84-1.34 0.82 0.96 0.70-1.32 0.21 1.35 0.84-2.16
TagSNPs               
CYP2D6_01t ¹N/A 0.32 0.33 0.89 0.71-1.12 0.3 0.91 0.77-1.08 0.97 1 0.79-1.25 0.65 0.93 0.66-1.3
CYP2D6_02t ¹N/A 0.46 0.07 1.21 0.98-1.49 0.98 1 0.86-1.17 0.89 0.98 0.79-1.22 0.43 0.88 0.65-1.20
CYP2D6_03t ¹N/A 0.24 0.18 0.84 0.65-1.08 0.93 1.01 0.84-1.21 0.93 1.01 0.79-1.30 0.93 1.02 0.72-1.43
CYP2D6_04t ¹N/A 0.08 0.34 1.19 0.83-1.72 0.34 0.86 0.63-1.17 0.88 1.03 0.70-1.52 0.43 1.25 0.72-2.19
CYP2D6_05t ¹N/A 0.22 0.41 0.9 0.69-1.16 0.94 1.01 0.83-1.22 0.48 0.91 0.69-1.18 0.6 1.1 0.77-1.59
  1. *Adjusted values in all cases, except PM models, include adjustment for grade, stage, chemotherapy, surgery, lymph node status, ER and tumour size.
  2. ** 95% CI, 95% confidence interval; ER, oestrogen receptor; MAF, mean allele frequency; SNP, single nucleotide polymorphisms.
  3. n/a, No calculations possible due to low sample number.
  4. §The PM group are classified as carriers of two variant alleles (rare homozygote alleles) for at least one of the functional SNPs associated with PM or intermediate metaboliser (IM) status. Where IM = CYP2D6*41; CYP2D6*9; CYP2D6*10 and PM = CYP2D6*4; CYP2D6*5; CYP2D6*6. In CYP2D6*Poor Metaboliser (PM) Model 1: the PM group (classified as stated) is compared with individuals who carried two copies of the wild-type allele (EM) at all SNPs (i.e. common homozygotes) or individuals who carried a single variant allele at a single SNP (heterozygotes). Adjusted values in all cases include adjustment for grade, stage, chemotherapy, surgery, tumour size and ER status.
  5. §§The PM group was classified as individuals carrying at least one variant allele at one or more of the functional SNPs (heterozygotes and rare homozygotes), associated with PM or intermediate metaboliser (IM) status. Where IM = CYP2D6*41; CYP2D6*9; CYP2D6*10 and PM = CYP2D6*4; CYP2D6*5; CYP2D6*6. In CYP2D6*Poor Metaboliser (PM) Model 2: the PM group (classified as stated) is compared with individuals who carried two copies of the wild-type allele (EM) at all SNPs (common homozygotes). Adjusted values in all cases include adjustment for grade, stage, chemotherapy, surgery, tumour size and ER status.
  6. ‡‡ N/A, not applicable.
  7. CYP2D6*6 refers to the 1976g > a variant, which is associated with CYP2D6*6b and CYP2D6*6c.