Table 5.

Multivariate linear regression analysis for factors affecting tamoxifen biotransformation in AIAN participants (n = 42)

Dependent	Independent	β‐coefficient ± SE	P value a
Endoxifen	Intercept	2.84 ± 6.07	0.6422
	CYP2D6 activity	3.60 ± 1.00	0.0010**
	CYP3A4 activity	‐2.08 ± 2.39	0.3895
	CYP3A5 activity	‐3.15 ± 3.17	0.3278
	CYP2C9 activity	0.60 ± 1.42	0.6745
	Age	0.05 ± 0.06	0.4539
	Recruitment site	‐0.74 ± 2.18	0.7355
4‐OH‐Tam	Intercept	0.57 ± 0.90	0.5263
	CYP2D6 activity	0.45 ± 0.16	0.0088*
	CYP3A4 activity	‐0.19 ± 0.35	0.5879
	CYP3A5 activity	‐0.54 ± 0.43	0.2246
	CYP2C9 activity	0.22 ± 0.21	0.2898
	Age	2.0 × 10−3 ± 0.01	0.8166
	Recruitment site	1.07 ± 0.45	0.0229*
N‐dm‐Tam	Intercept	133.64 ± 95.66	0.1712
	CYP2D6 activity	‐9.70 ± 19.03	0.6134
	CYP3A4 activity	‐5.61 ± 34.83	0.8729
	CYP3A5 activity	‐6.78 ± 49.26	0.8914
	CYP2C9 activity	‐13.37 ± 24.57	0.5897
	Age	0.91 ± 0.85	0.2897
	Recruitment site	171.41 ± 50.89	0.0019*
Tamoxifen	Intercept	81.30 ± 64.40	0.2151
	CYP2D6 activity	5.08 ± 9.78	0.6066
	CYP3A4 activity	‐19.84 ± 22.65	0.3869
	CYP3A5 activity	‐16.67 ± 33.95	0.6264
	CYP2C9 activity	‐10.87 ± 15.26	0.4812
	Age	0.83 ± 0.64	0.2008
	Recruitment site	81.46 ± 28.09	0.0064*
Endoxifen / tamoxifen	Intercept	0.08 ± 0.05	0.1328
	CYP2D6 activity	0.04 ± 0.01	4.4 × 10−7 ***
	CYP3A4 activity	‐0.02 ± 0.01	0.0874
	CYP3A5 activity	‐0.05 ± 0.01	0.0020*
	CYP2C9 activity	4.8 × 10−3 ± 0.02	0.7599
	Age	‐3.1 × 10−4 ± 4.3 × 10−4	0.4857
	Recruitment site	‐0.05 ± 0.01	0.0001**
4‐OH‐Tam / tamoxifen	Intercept	0.01 ± 0.01	0.1944
	CYP2D6 activity	4.6 × 10−3 ± 7.4 × 10−4	5.3 × 10−7 ***
	CYP3A4 activity	5.7 × 10−4 ± 1.1 × 10−3	0.6167
	CYP3A5 activity	‐4.5 × 10−3 ± 1.9 × 10−3	0.0216*
	CYP2C9 activity	4.5 × 10‐3 ± 2.0 × 10−3	0.0318*
	Age	‐1.1 × 10−4 ± 6.5 × 10−5	0.1010
	Recruitment site	‐2.9 × 10−3 ± 1.5 × 10−3	0.0699
N‐dm‐Tam / tamoxifen	Intercept	2.08 ± 0.58	0.0010**
	CYP2D6 activity	‐0.32 ± 0.13	0.0247*
	CYP3A4 activity	0.15 ± 0.16	0.3435
	CYP3A5 activity	‐0.04 ± 0.36	0.9048
	CYP2C9 activity	0.14 ± 0.10	0.1882
	Age	‐0.01 ± 4.4 × 10−3	0.1700
	Recruitment site	0.11 ± 0.16	0.4916
Endoxifen / 4‐OH‐Tam	Intercept	6.36 ± 1.27	1.5 × 10−5 ***
	CYP2D6 activity	1.40 ± 0.33	0.0002**
	CYP3A4 activity	‐1.08 ± 0.33	0.0028*
	CYP3A5 activity	‐0.93 ± 0.69	0.1854
	CYP2C9 activity	‐1.20 ± 0.38	0.0034*
	Age	0.01 ± 0.01	0.1995
	Recruitment site	‐2.04 ± 0.36	1.9 × 10−6 ***
Endoxifen / N‐dm‐Tam	Intercept	0.03 ± 0.04	0.4941
	CYP2D6 activity	0.03 ± 4.1 × 10−3	3.0 × 10−8 ***
	CYP3A4 activity	‐0.01 ± 0.01	0.1180
	CYP3A5 activity	‐0.02 ± 0.01	0.1388
	CYP2C9 activity	4.2 × 10−3 ± 0.01	0.6346
	Age	1.3 × 10−4 ± 3.3 × 10−4	0.6937
	Recruitment site	‐0.03 ± 0.01	0.0001**

4‐OH‐Tam, 4‐hydroxytamoxifen; AIAN, American Indian Alaska Native; CYP, cytochrome P450; N‐dm‐Tam, N‐desmethyltamoxifen.

^aLinear regression analysis using robust standard errors adjusted for age and recruitment site.

Significant associations: ^* P ≤ 0.05; ^** P ≤ 0.001; ^*** P ≤ 0.0001.