Phase I/II enzyme gene polymorphisms and esophageal cancer risk: A meta-analysis of the literature

Table 1 Summary of studies included in the analysis of CYP1A1, CYP2E1, GASTM1, GSTT1 and GSTP1.

Study	Yr	Study design	Cases Mean age	Controls Mean age	Cases Man (%)	Controls Man (%)	Polymorphisms	Result	Adjusted factors	Reference
Hori H	1997	2	NA	NA	78 (83)	NA	CYP1A1, MspI	NS		42
							CYP1A1, IIe-Val	NS
							GSTM1	NS
							CYP2E1, Rsal	NS
Nimura Y	1997	1	NA	NA	67 (75)	76 (55)	CYP1A1, IIe-Val	S		43
							GSTM1	NS
Morita S	1997	2	62.2	50.5	45 (85)	112 (85)	CYP1A1, IIe-Val	NS		44
							CYP2E1, Rsal	NS
							GSTM1	NS
Morita S	1998	2	62.1	49.8	56 (85)	102 (62)	GSTP1	S		45
Lin DX	1998	NA	55.5	53.3	27 (60)	23 (50)	CYP2E1, Rsal	S	Adjusted by age and sex	36
							CYP2E1,Dral	NS
							GSTM1	NS
							GSTT1	NS
							GSTP1	NS
Van Lieshout EM	1999	2	NA	52	27 (79)	98 (40)	CYP1A1, MspI	S	46
							CYP1A1, IIe-Val	NS
							GSTM1	NS
							GSTT1	NS
							GSTP1	S
Shao G	2000	2	55	53	74 (69)	80 (72)	CYP1A1, IIe-Val	NS		47
							GSTM1	S
Lee JM	2000	2	NA	NA	82 (91)	228 (89)	GSTP1	NS	Adjusted by potential factors	48
Tan W	2000	2	54.5	53.6	99 (66)	99 (66)	CYP2E1, Rsal	S	Adjusted by age, sex and smoking	49
							GSTM1	S
							GSTT1	NS
							GSTP1	NS
Wu M-T	2002	1	60.6	61.2	133 (91)	298 (92)	CYP1A1, MspI	NS	Adjusted by age, sex, smoking and alcohol, etc.	50
							CYP1A1, IIe-Val	S
Gao CM	2002	2	NA	NA	55 (59)	131 (66)	CYP2E1, Rsal	NS	Adjusted by age, sex and potential factors	51
Yokoyama A	2002	2	61.7	58.8	234 (100)	634 (100)	GSTM1	NS		52
Gao CM	2002	2	NA	NA	78 (55)	149 (67)	GSTM1	S	Adjusted by age and sex	53
							GSTT1	NS
Wang LD	2003	2	NA	NA	32 (53)	NA	CYP1A1, MspI	NS		54
							CYP1A1, IIe-Val	NS
							GSTM1	NS
							GSTT1	NS
							GSTP1	NS
Casson AG	2003	2	NA	NA	38 (84)	38 (84)	CYP1A1, MspI	NS	Adjusted by age, sex and smoking	55
							CYP1A1, IIe-Val	NS
							GSTM1	NS
							GSTT1	NS
							GSTP1	S
Wang AH	2004	1	NA	NA	97 (76)	78 (77)	CYP1A1, IIe-Val	S		37
							GSTM1	S

1: Population-based case-control study, 2: hospital-based case-control study. NA, not available; NS, not significant (P>0.05); S, significant (P<0.05).

Table 2 Summary of the meta-analysis of CYP1A1, CYP2E1, GSTP1 and esophageal cancer risk.

Study	Country	Cases	Control	Cases wt/wt	Cases hetero1	Cases homo1	Control wt/wt1	Control hetero1	Control homo1	OR1 (95%CI)23	OR2 (95%CI)23	OR3 (95%CI)23
CYP1A1 Ile-Val:
Hori H	Japan	91	428	52	37	2	275	133	20	1.47 (0.89-2.41)	0.53 (0.06-2.29)	1.35 (0.83-2.19)
Nimura Y	China	89	137	50	26	13	92	38	7	1.26 (0.65-2.41)	3.42 (1.17-10.72)	1.59 (0.89-2.87)
Morita S	Japan	53	132	32	20	1	80	49	3	1.02 (0.49-2.08)	0.83 (0.02-10.84)	1.0 (0.5-1.9)
van Lieshout EM	Netherlands	34	247	26	8	0	207	37	3	1.72 (0.62-4.30)	0 (0-10.62)	1.59 (0.58-3.95)
Shao G	China	107	111	43	56	8	55	51	5	1.40 (0.78-2.53)	2.05 (0.54-8.49)	1.46 (0.83-2.59)
Wu M-T	Taiwan	146	324	68	62	16	179	127	18	1.34 (0.86-2.07)4	2.48 (1.15-5.34)4	1.42 (0.94-2.14)
Wang LD	China	62	38	30	28	4	20	16	2	1.17 (0.47-2.93)	1.33 (0.17-15.97)	1.19 (0.49-2.88)
Casson AG	Canada	45	45	45	0	0	45	0	0	NA6	NA6	NA6
Wang AH	China	127	101	21	56	50	31	48	22	1.72 (0.83-3.58)	3.35 (1.49-7.61)	2.24 (1.14-4.43)
Meta-analysis results		754	1563	367	293	94	984	499	80	1.37 (1.09-1.71)	2.52 (1.62-3.91)	1.44 (1.17-1.78)
CYP1A1 MspI:
Hori H	Japan	94	242	33	50	11	106	97	39	1.66 (0.96-2.88)	0.91 (0.38-2.06)	1.44 (0.86-2.44)
van Lieshout EM	Netherlands	34	247	22	12	0	207	37	3	3.05 (1.26-7.08)	0 (0-12.63)	2.82 (1.17-6.51)
Wu M-T	Taiwan	146	324	60	65	21	136	146	42	0.98 (0.63-1.53)4	1.24 (0.65-2.36)4	1.04 (0.68-1.57)
Casson AG	Canada	45	45	38	NA	NA	33	NA	NA	NA	NA	0.6 (0.2-1.8)4
Wang LD	China	62	38	33	25	4	12	22	4	0.41 (0.16-1.08)	0.36 (0.06-2.33)	0.41 (0.16-1.02)
Meta-analysis results		381	896	186	152	36	494	302	88	1.21 (0.64-2.32)	1.02 (0.62-1.68)	1.07 (0.64-1.80)
CYP2E1:
Hori H	Japan	79	633	49	24	6	412	202	19	1.00 (0.57-1.72)	2.66 (0.83-7.33)	1.14 (0.68-1.89)
Morita S	Japan	53	132	34	18	1	85	42	5	1.07 (0.51-2.22)	0.50 (0.01-4.72)	1.0 (0.5-2.0)
Lin DX	China	45	45	36	6	3	20	22	3	0.15 (0.04-0.48)	0.56 (0.07-4.59)	0.21 (0.08-0.56)4,5
Tan W	China	150	150	107	31	12	66	77	7	0.25 (0.14-0.43)	1.06 (0.36-3.34)	0.31 (0.24-0.40)4,5
Gao CM	China	93	196	55	31	7	121	62	13	1.13 (0.60-2.13)4	1.23 (0.40-3.77)4	1.15 (0.64-2.07)4
Meta-analysis results		420	1156	281	110	29	704	405	47	0.59 (0.28-1.23)	1.33 (0.72-2.44)	0.63 (0.30-1.30)
GSTP1:
Morita S	Japan	66	164	61	5	0	113	48	3	0.19 (0.07-0.52)	0 (0-4.6)	0.13 (0.04-0.45)5
Lin DX	China	42	36	29	12	1	22	11	3	0.83 (0.28-2.51)	0.25 (0.005-3.48)	0.7 (0.3-1.8)
van Lieshout EM	Netherlands	34	247	10	21	3	146	89	12	3.44 (1.47-8.55)	3.65 (0.56-16.82)	3.47 (1.51-8.46)
Lee JM	Taiwan	90	254	65	NA	NA	160	NA	NA	NA6	NA6	0.65 (0.39-1.11)4,5
Tan W	China	150	150	93	48	9	91	53	6	0.89 (0.53-1.48)	0.95 (0.58-1.55)	1.0 (0.8-1.3)
Wang LD	China	62	38	29	30	3	24	13	1	1.91 (0.76-4.89)	2.48 (0.18-135.66)	1.95 (0.79-4.87)4
Casson AG	Canada	45	45	19	22	4	26	12	7	2.5 (1.0-6.3)	0.8 (0.2-3.1)	1.8 (0.8-4.3)4
Meta-analysis results		489	934	306	138	20	582	226	32	1.17 (0.55-2.49)	1.02 (0.65-1.58)	1.01 (0.60-1.70)

¹“wt” allele was defined for each polymorphism as follows: the IIe allele for CYP1A1 IIe-Val and GSTP1 Ile-Val, the *1 allele for CYP1A1 MspI, and c1 for CYP2E1. Non-“wt” allele was defined as follows: the Val allele for CYP1A1 IIe-Val and GSTP1 Ile-Val, the *2 allele for CYP1A1 MspI and c2 for CYP2E1. “wt/wt”, “hetero”, and “homo” indicate homozygous for “wt” allele, heterozygous, and homozygous for non-“wt” allele, respectively.

²“wt/wt” was defined as the reference group and OR1, OR2, and OR3 for heterozygous, non-“wt” homozygous and the combination of heterozygous and non-“wt” homozygous groups.

³All the ORs were crude values calculated from the genotype distribution except in places denoted by^4,5.

⁴indicates cases where adjusted OR in the report was used and 5indicates where the OR value was inverted.

⁶NA: not available.

Table 3 Summary of the meta-analysis of GSTM1, GSTTI and esophageal cancer risk.

Study	Country	Cases	Controls	Case	Case	Control	Control	OR (95%CI)
GSTM1:				Non-null	Null	Non-null	Null
Hori H	Japan	94	428	53	41	232	196	0.92 (0.57-1.47)
Nimura Y	China	89	137	42	47	74	63	1.31 (0.74-2.32)
Morita S	Japan	53	132	30	23	77	55	1.1 (0.6-2.0)
Lin DX	China	45	45	25	20	24	21	1.0 (0.4-2.3)3
van Lieshout EM	Netherlands	34	247	17	17	119	128	0.93 (0.42-2.04)
Shao G	China	107	111	68	39	56	55	1.76 (1.03-2.74)
Tan W	China	150	150	104	46	74	76	0.43 (0.33-0.56)34
Yokoyama A	Japan	234	634	131	103	313	321	0.77 (0.56-1.05)
Gao CM	China	141	223	35	106	90	133	2.17 (1.35-3.50)3
Wang LD	China	62	38	35	27	19	19	0.77 (0.32-1.88)
Casson AG	Canada	45	45	19	26	20	25	1.1 (0.5-2.7)3
Wang AH	China	127	101	53	74	57	44	1.81 (1.03-3.18)
Meta-analysis	results	1181	2291	612	569	1155	1136	1.07 (0.76-1.51)
GSTT1:
Lin DX	China	45	45	26	19	22	23	0.7 (0.3-1.5)3
van Lieshout EM	Netherlands	34	247	28	6	198	49	0.87 (0.28-2.29)
Tan W	China	150	150	90	60	91	59	1.11 (0.83-1.43)34
Gao CM	China	141	223	67	74	104	119	0.90 (0.59-1.39)3
Wang LD	China	62	38	28	34	18	20	1.09 (0.45-2.65)
Casson AG	Canada	45	45	37	8	33	12	0.6 (0.2-1.7)3
Meta-analysis results		477	748	276	201	466	282	0.99 (0.80-1.22)

¹Non-null genotype as the reference group. ²All the ORs were crude values calculated from the genotype distribution except in places denoted by^{3, 4}.

³indicates cases where the adjusted OR in the report was used and

⁴where the OR value was inverted.

Table 4 Results of meta-regression analysis and Egger’s test for publication bias.

	Number of studies	Egger’s test Forpublicationbias1 P	Results of meta-regression test
			Asian Yes/no Coefficient3	Chinese Yes/no Coefficient3	Publication Year Coefficient3	Design 1 or 22 Coefficient3	Matching Yes/no Coefficient3
CYP1A1 Ile-Val	8	0.96	-0.1	0.19	0.11	-0.2	-0.22
CYP1A1 MspI	5	0.96	-0.42	-0.67	-0.9	0.01	-0.01
CYP2E RsaI	5	0.32	1	-0.89	0.76	1.3	-0.13
GSTM1	12	0.04	0.06	0.21	0.25	-0.34	-0.16
GSTT1	6	0.11	0.34	0.34	-0.16	0.37	0.16
GSTP1	7	0.99	-1.254	-0.07	0.88	0.4	0.02

¹P-value of Egger’s test for publication bias. ²Study design: 1: population-based case-control study, 2: hospital-based case-control study.

³Coefficient in the meta-regression analysis indicates the summary OR change in the value for that factor. For example, the OR for studies examining CYP1A1 Ile-Val polymorphism only among Asian population is the value of (summary OR-0.1). ⁴Indicates statistical significance at the level of P<0.10.