Link between colorectal cancer and polymorphisms in the uridine-diphosphoglucuronosyltransferase 1A7 and 1A1 genes

Table 1 OR and 95%CI for CRC with UGT1A7 genotypes and alleles.

UGT1A7 genotype or allele	Number (%)		OR (95%CI)	P
	Cases (n = 268)	Controls (n = 441)
UGT1A7*1/*1	76 (28.4)	184 (41.7)	0.55 (0.40-0.77)	<0.001
UGT1A7*1/*2	73 (27.2)	117 (26.5)	1.04 (0.74-1.46)	0.84
UGT1A7*1/*3	77 (28.7)	75 (17.0)	1.97 (1.37-2.83)	<0.001
UGT1A7*2/*2	9 (3.4)	22 (5.0)	0.66 (0.30-1.46)	0.31
UGT1A7*2/*3	23 (8.6)	32 (7.3)	1.20 (0.69-2.10)	0.52
UGT1A7*3/*3	10 (3.7)	11 (2.5)	1.52 (0.64-3.62)	0.35
UGT1A7*1	226 (84.3)	376 (85.3)	1.08 (0.71-1.64)	0.74
UGT1A7*2	105 (39.2)	171 (38.8)	1.02 (0.75-1.39)	0.92
UGT1A7*3	110 (41.0)	118 (26.8)	1.91 (1.38-2.63)	<0.001

Table 2 The comparisons between the observed percentage with the expected percentage of control subjects carrying UGT1A7*1/*2, UGT1A7*1/*3, and UGT1A7*2/*3 genotypes.

	Control subjects (n = 441)		χ2	P
	Observed percentage (%)	Expected percentage (%)1
UGT1A7*1/*2	26.5	28.9	0.081	0.960
UGT1A7*1/*3	17.0	20.4
UGT1A7*2/*3	7.3	7.1

¹The expected percentage was calculated by the Hardy-Weinberg equilibrium. For example, expected percentage of UGT1A7*1/*2 = 2×(frequency of UGT1A7*1/*1)^1/2×(frequency of UGT1A7*2/*2)^1/2 = 2×41.7^1/2×5.0^1/2 = 28.9%.

Table 3 The comparison of UGT1A1 genotypes between case and control groups.

UGT1A1 genotype	Case group (n = 268)		Control group (n = 441)		P (χ2 test)
	Number	%	Number	%
Wild type	121	45.2	218	49.4	0.78
Heterozygous variation	118	44.0	186	42.23
6/71	37		96
211 G to A/normal	76		79
1091 C to T/normal	5		11
Compound heterozygous variation	23	8.6	34	7.7
6/7, 211 G to A/normal	13		6
6/7, 686 C to A/normal	8		20
6/7, 1091 C to T/normal	0		2
6/7, 211 G to A/normal,	1		2
686 C to A/normal 6/7,
686 C to A/normal,	1		0
1091 C to T/normal
211 G to A/normal,	0		4
1091 C to T/normal
Homozygous variation	6	2.2	3	0.7
7/72	1		0
211 G to A/211 G to A	4		3
7/7, 211 G to A/normal	1		0

¹6/7 and

²7/7 represent A(TA)₆TAA/A(TA)₇TAA and A(TA)₇TAA/A(TA)₇TAA in the promoter area of UGT1A1 gene, respectively.

³The expected frequency is 40.7% calculated by Hardy-Weinberg equilibrium: [2×(frequency of wild type)^1/2×(frequency of compound heterozygous variation plus frequency of homozygous variation)^1/2 = 2×49.4^1/2×(7.7+0.7)^1/2 = 40.7]. The observed frequency (42.2%) is not significantly different from the expected frequency (40.7%) (P = 0.89 by χ² test).

Table 4 OR and 95%CI for CRC with UGT1A1 alleles.

UGT1A1 allele	Number (%)		OR (95%CI)	P
	Cases (n = 268)	Controls (n = 441)
A(TA)7TAA	62 (23.1)	126 (28.6)	0.75 (0.52-1.05)	0.09
Variant-211	95 (35.4)	94 (21.3)	2.03 (1.45-2.84)	<0.001
Variant 686	10 (3.7)	22 (5.0)	0.74 (0.34-1.58)	0.44
Variant 1091	6 (2.2)	17 (3.8)	0.57 (0.22-1.47)	0.25

Table 5 The interaction effect of the UGT1A7*3 allele and variant-211 UGT1A1 allele upon the development of CRC.

UGT1A7*3/ variant-211UGT1A1	Number (%)		OR (95%CI)	P
	Cases (n = 268)	Controls (n = 441)
Absent/absent	145 (54.1)	302 (68.5)	1.00
Present/absent	28 (10.4)	45 (10.2)	1.30 (0.78-2.16)	0.39
Absent/present	13 (4.8)	21 (4.8)	1.29 (0.63-2.65)	0.33
Present/present	82 (30.6)	73 (16.5)	2.34 (1.61-3.40)	<0.001
Expected by additive1		1.59

¹Expected OR under no-interaction additive model.

Table 6 OR and 95%CI of stages-C and -D CRCs with CRC-related UGT1A alleles.

CRC-related allele	Stage of CRC		OR (95%CI)	P
	C and D (n = 93)	A and B(n = 175)
UGT1A7*3	611 (65.6%)	49 (28.0%)	4.90 (2.86-8.41)	<0.001
Variant-211 UGT1A1	551 (59.1%)	40 (22.9%)	4.89 (2.84-8.41)	<0.001

¹All the subjects were stage-C patients, except two were stage-D patients.

Table 7 Adjusted odds ratios (AOR) and 95%CI for the different stages of CRC with age, gender, and CRC-related UGT1A alleles.

Factor	CRC stage		OR (95%CI)	P
	C and D (n = 93)	A and B (n = 175)
Age >51/ ≤50 yr	79/14	155/20	0.68 (0.31-1.53)	0.35
Gender male/female	55/38	85/90	1.44 (0.82-2.51)	0.20
UGT1A7*3	61 (65.6%)	49 (28.0%)	2.51 (1.23-5.13)	0.01
Variant-211 UGT1A1	55 (59.1%)	40 (22.9%)	2.71 (1.31-5.58)	0.01

Table 8 The interaction effect of the UGT1A7*3 allele and variant-211 UGT1A1 allele upon the stage of CRC.

UGT1A7*3/variant-211UGT1A1	CRC stage		OR (95%CI)	P
	C and D (n = 93)	A and B (n = 175)
Absent/absent	27 (29.0%)	118 (67.4%)	1.00
Present/absent	11 (11.8%)	17 (9.7%)	2.83 (1.19-6.72)	0.02
Absent/present	5 (5.4%)	8 (4.6%)	2.73 (0.83-9.01)	0.10
Present/present	50 (53.8%)	32 (18.3%)	6.83 (3.71-12.56)	<0.001
Expected by additive1		4.56

¹Expected OR under no-interaction additive model.