. Author manuscript; available in PMC: 2016 Feb 1.

Published in final edited form as: Pharmacogenomics J. 2015 Apr 14;16(1):54–59. doi: 10.1038/tpj.2015.23

Table 2.

Univariate analyses of the associations between genetic variants and phenotypes

Variant	Reference	Discovery cohort (n = 67)			Replication cohort (n = 74–103)
Variant	Reference	Estimate ± s.e.	95% CI	P-value	n	Estimate ± s.e.	P-value
Log₁₀ ANC Nadir
ABCC1 IVS11 -48 (C>T)	CC/CT	− 0489±0.201	(−0.095, − 0.883)	0.018	74	0.053± 0.117	0.652
UGT1A128 (TA6>TA7*)	11=1 128=2	− 0.257±0.061	(−0.137, − 0.377)	<0.001	75	− 0.139±0.081	0.090
UGT1A128 (TA6>TA7*)	2828=3	− 0.257±0.061	(−0.137, − 0.377)	<0.001	75	− 0.139±0.081	0.090
UGT1A193 (G>A)*	GG/AG	− 0.607±0.129	(−0.354, − 0.860)	< 0.001	103	− 0.417±0.170	0.016
SLCO1B11b (A>G)*	AA	0.240±0.106	(0.032, 0.448)	0.027	84	0.278±0.107	0.012
Log₁₀ irinotecan AUC_0-24
ABCC2 –24 (C>T)	CC	0.090±0.035	(0.021, 0.159)	0.012	94	0.067±0.030	0.040
SLCO1B1*5(T>C)	TT	0.084±0.036	(0.013, 0.155)	0.023	83	− 0.010±0.035	0.769
Log₁₀SN-38 AUC_0-24
UGT1A128* (TA6>TA7)	11= 1	0.140±0.046	(0.050, 0.190)	0.004	75	0.189±0.043	<0.001
	128=2
	2828= 3
UGT1A193* (G>A)	GG= 1	0.130±0.047	(0.038, 0.222)	0.007	103	0.171±0.033	<0.001
	AG=2
	AA=3
ABCB1 IVS9 –44 (A>G)	AA	− 0.180±0.070	(−0.043, -0.317)	0.013	77	0.021±0.054	0.703
Log₁₀ SN-38G AUC_0-24
ABCC2 3972 (C> T)	CC/CT	0.250±0.100	(0.054, 0.446)	0.019	105	− 0.104±0.086	0.232
Log₁₀ SN-38G AUC_0-24 /Log₁₀ SN-38 AUC_0-24
ABCC1 1684 (T >C)	TT	− 0.316±0.153	(−0.016, − 0.616)	0.043	95	− 0.052±0.059^*	0.382
UGT1A128 (TA6>TA7)*	11= 1	− 0.170±0.048	(−0.076, − 0.264)	<0.001	103	− 0.243±0.053	<0.001
	128=2
	2828= 3
UGT1A193 (G > A)*	GG= 1	− 0.150±0.051	(−0.050, − 0.250)	0.004	75	− 0.214±0.042	<0.001
	AG=2
	AA=3

Abbreviations: ANC, absolute neutrophil count; AUC, area under the concentration–time curve; CI, confidence interval. Data were adjusted for age, sex and dose (mg m⁻²). ANC nadir was also adjusted for baseline ANC. The genotype reference groups were the same for all discovery and replication cohort analyses, with the exception of ABCC1 IVS11 -48C>T and ANC nadir. For ABCC1 IVS11 -48C>T and ANC nadir in the replication cohort, the reference genotype was only CC, as there were no TT genotypes. The estimates of effect of replicated variants are denoted in bold. The number of patients genotyped per variant in the replication cohort varied due to insufficient DNA quantity.

Although the association between ABCC1 1684T>C (dominant model) and glucuronidation ratio satisfies our criteria for replication, we are less convinced of the association, given the 84% reduction in the magnitude of the estimate as compared with that of the discovery cohort.