Polymorphism of genes encoding drug-metabolizing and inflammation-related enzymes for susceptibility to cholangiocarcinoma in Thailand

Table 1 Number of subjects with non-missing and with missing values for serum anti-Opisthorchis viverrini, alcohol consumption, and smoking dependent on each matched-pair analysis

Principle independent variable	Number of matched pairs	Anti-OV		Alcohol consumption		Smoking
		Missing	Non-missing	Missing	Non-missing	Missing	Non-missing
Anti-OV	95	Not applicable		3	187	2	188
GSTM1	95	10	180	2	188	2	188
GSTT1	95	10	180	2	188	2	188
CYP2E1	93	9	177	2	184	2	184
IL6, -634 G/C	91	10	172	2	180	2	180
IL6, -175 G/C	92	10	174	2	182	2	182
IL10, -819 T/C	91	10	172	2	180	2	180
NF-kB, -94 ins/del ATTG	92	10	174	2	182	2	182

OV: Opisthorchis viverrini.

Table 2 Relationship between serum anti-Opisthorchis viverrini and cholangiocarcinoma risk, Ubon Ratchathani, Thailand

Number of case-control pairs according to serum anti-OV status: positive (+) vs negative (-)				Crude OR	95%CI		P value	Adjusted1 OR	95%CI		P value	Adjusted2 OR	95%CI		P value
Case (+) / Control (+)	Case (+) / Control (-)	Case (-) / Control (+)	Case (-) / Control (-)		LL	UL			LL	UL			LL	UL
67	23	2	3	11.50	2.71	48.78	< 0.001	8.96	2.06	38.99	0.001	9.40	2.16	40.85	0.003

¹Adjusted for alcohol consumption and smoking.

²Adjusted for alcohol consumption and smoking. Missing values for these variables were imputed.

OV: Opisthorchis viverrini; CCA: Cholangiocarcinoma; LL: Lower limit; UL: Upper limit.

Table 3 Relationship between serum anti-Opisthorchis viverrini, alcohol consumption, and smoking and cholangiocarcinoma risk, Ubon Ratchathani, Thailand, shown by analysis for each of the genetic polymorphisms

Independent variable	Gene adjusted for	Adjusted1 OR	95%CI		P value	Adjusted2 OR	95%CI		P value
			LL	UL			LL	UL
Positive serum anti-OV	GSTM1	9.16	2.00	41.90	0.004	7.12	1.76	28.81	0.006
	GSTT1	8.16	1.85	35.96	0.006	7.33	1.74	30.93	0.007
	CYP2E1	7.75	1.73	34.69	0.007	4.90	1.41	17.05	0.013
	IL-6, -174 G/C	8.07	1.80	36.07	0.006	5.39	1.51	19.29	0.010
	IL-6, -634 G/C	7.21	1.57	32.98	0.011	6.13	1.54	24.32	0.010
	IL-10, -819 T/C	9.04	1.97	41.39	0.005	6.03	1.65	22.04	0.007
	NF-kB	11.81	2.31	60.44	0.003	8.14	1.90	34.90	0.005
Alcohol drinking	GSTM1	1.06	0.70	1.60	0.779	1.12	0.76	1.67	0.560
	GSTT1	1.05	0.70	1.58	0.817	1.10	0.74	1.63	0.643
	CYP2E1	1.05	0.70	1.58	0.801	1.10	0.75	1.63	0.614
	IL-6, -174 G/C	1.03	0.68	1.56	0.907	1.09	0.73	1.62	0.674
	IL-6, -634 G/C	1.00	0.65	1.52	0.989	1.06	0.70	1.59	0.784
	IL-10, -819 T/C	0.98	0.63	1.53	0.933	1.06	0.70	1.61	0.785
	NF-kB	0.99	0.63	1.54	0.956	1.05	0.68	1.60	0.836
Smoking	GSTM1	1.56	1.01	2.40	0.044	1.49	0.99	2.23	0.053
	GSTT1	1.56	1.01	2.42	0.044	1.51	1.00	2.27	0.049
	CYP2E1	1.55	1.00	2.41	0.052	1.46	0.98	2.18	0.060
	IL-6, -174 G/C	1.73	1.05	2.85	0.030	1.62	1.04	2.54	0.035
	IL-6, -634 G/C	1.79	1.10	2.91	0.018	1.73	1.08	2.76	0.022
	IL-10, -819 T/C	1.80	1.09	2.98	0.022	1.65	1.05	2.59	0.030
	NF-kB	1.78	1.08	2.94	0.023	1.80	1.11	2.91	0.016

¹Adjusted for alcohol consumption and smoking.

²Adjusted for alcohol consumption and smoking. Missing values for these variables were imputed.

OV: Opisthorchis viverrini; CCA: Cholangiocarcinoma; LL: Lower limit; UL: Upper limit.

Table 4 Relationship between polymorphisms of drug-metabolizing and inflammation-related enzyme genes and cholangiocarcinoma risk, Ubon Ratchathani, Thailand

Gene	Number of pairs according to gene polymorphism of case and control					Polymorphism	Crude OR	95%CI		P value	Adjusted1 OR	95%CI		P value	Adjusted2 OR	95%CI		P value
								LL	UL			LL	UL			LL	UL
GSTM1
			Case
			Wild	Null
	Control	Wild	8	18		Wild	1.00	Reference			1.00	Reference			1.00	Reference
		Null	18	51		Null	1.00	0.52	1.92	1.000	0.67	0.29	1.56	0.357	0.81	0.37	1.75	0.594
GSTT1
			Case
			Wild	Null
	Control	Wild	44	23		Wild	1.00	Reference			1.00	Reference			1.00	Reference
		Null	21	7		Null	1.10	0.61	1.98	0.763	0.94	0.44	1.98	0.865	1.02	0.52	2.02	0.957
CYP2E1
			Case
			c1/c1	c1/c2	c2/c2
	Control	c1/c1	56	14	4	c1/c1	1.00	Reference			1.00	Reference			1.00	Reference
		c1/c2	12	4	2	c1/c2	1.11	0.52	2.38	0.782	1.02	0.39	2.70	0.966	1.14	0.47	2.77	0.773
		c2/c2	1	0	0	c2/c2	6.19	0.74	52.08	0.093	2.02	0.20	20.67	0.552	4.17	0.45	38.24	0.207
						c1/c2 or c2/c2	1.38	0.68	2.83	0.371	1.14	0.47	2.77	0.767	1.35	0.58	3.11	0.484
IL-6
			Case			-174
			G/G	G/C	C/C
	Control	G/G	90	0	0	G/G	1.00	Reference			1.00	Reference			1.00	Reference
		G/C	1	0	0	G/C	0.00	-	-	-	0.003	0.00	-	0.995	0.0037	0.00	-	0.999
		C/C	0	0	0	C/C	-	-	-	-	-	-	-	-	-	-	-	-
IL-6						-634
			Case
			G/G	G/C	C/C
	Control	G/G	0	4	5	G/G	1.00	Reference			1.00	Reference			1.00	Reference
		G/C	2	13	12	G/C	1.93	0.63	5.93	0.252	1.90	0.49	7.30	0.351	1.69	0.46	6.25	0.432
		C/C	4	18	34	C/C	1.28	0.44	3.73	0.654	1.38	0.40	4.71	0.607	1.45	0.43	4.87	0.551
						G/C or C/C	1.50	0.53	4.21	0.442	1.53	0.46	5.05	0.488	1.52	0.46	4.98	0.489
IL-10						-819 T/C
			Case
			T/T	T/C	C/C
	Control	T/T	23	15	6	T/T	1.00	Reference			1.00	Reference			1.00	Reference
		T/C	15	17	4	T/C	0.81	0.41	1.60	0.537	0.66	0.27	1.63	0.371	0.75	0.34	1.70	0.497
		C/C	8	0	3	C/C	1.19	0.46	3.06	0.715	1.59	0.43	5.93	0.487	1.63	0.51	5.17	0.405
						T/C or C/C	0.91	0.51	1.65	0.763	0.85	0.39	1.87	0.686	0.95	0.47	1.93	0.891
NF-kB						-94 ins/del ATTG
			Case
			del/del	ins/del	ins/ins
	Control	del/del	3	5	3	del/del	1.00	Reference			1.00	Reference			1.00	Reference
		ins/del	4	16	13	ins/del	0.83	0.32	2.17	0.711	1.11	0.27	4.61	0.884	0.79	0.24	2.67	0.708
		ins/ins	9	20	19	ins/ins	0.48	0.19	1.23	0.128	0.32	0.08	1.20	0.090	0.33	0.10	1.03	0.057
						ins/del or ins/ins	0.91	0.51	1.65	0.763	0.49	0.14	1.69	0.258	0.47	0.16	1.38	0.167

¹Adjusted for alcohol consumption and smoking.

²Adjusted for alcohol consumption and smoking. Missing values for these variables were imputed.

CCA: Cholangiocarcinoma; LL: Lower limit; UL: Upper limit.

Table 5 Risk of cholangiocarcinoma due to the combination of polymorphisms of GSTT1 and CYP2E1: Matched case-control study, Ubon Ratchathani, Thailand

CYP2E1	GSTT1 wild		GSTT1 null		CYP2E1	GSTT1 wild				GSTT1 null
	Number		Number			Odds ratio1	95%CI		P value	Odds ratio1	95%CI		P value	P for interaction
	Case	Control	Case	Control			LL	UL			LL	UL
c1/c1	49	59	25	18	c1/c1	1.00	Reference			2.04	0.95	4.39	0.07	< 0.01
c1/c2 + c2/c2	24	9	5	11	c1/c2 + c2/c2	3.33	1.23	9.00	0.02	0.54	0.14	2.13	0.38

¹Based on the conditional logistic regression model.

CCA: Cholangiocarcinoma; CI: Confidence interval; LL: Lower limit; UL: Upper limit.