Table 2

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

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

*Adjusted values in all cases, except PM models, include adjustment for grade, stage, chemotherapy, surgery, lymph node status, ER and tumour size.

** 95% CI, 95% confidence interval; ER, oestrogen receptor; MAF, mean allele frequency; SNP, single nucleotide polymorphisms.

†n/a, No calculations possible due to low sample number.

§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.

§§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.

‡‡ N/A, not applicable.

‡CYP2D6*6 refers to the 1976g > a variant, which is associated with CYP2D6*6b and CYP2D6*6c.

Abraham et al. Breast Cancer Research 2010 12:R64   doi:10.1186/bcr2629

Open Data