CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

doi:10.3748/wjg.v22.i45.9974

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World Journal of Gastroenterology

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1007-9327

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Case Control Study

World J Gastroenterol. Dec 7, 2016; 22(45): 9974-9983
Published online Dec 7, 2016. doi: 10.3748/wjg.v22.i45.9974

Table 1 Sociodemographic data of patients with sporadic colorectal cancer and controls n (%)

Variables	Control	Case	OR¹	95%CI	P value
Variables	(n = 400)	(n = 227)	OR¹	95%CI	P value
Gender
Female	125 (31.3)	106 (46.7)	1.00 (reference)
Male	275 (69.7)	121 (53.3)	0.55	0.35-0.85	< 0.01²
Age (mean)
< 62	350 (87.5)	105 (46.3)	1.00 (reference)
≥ 62	50 (12.5)	122 (53.7)	7.54	4.94-11.50	< 0.01²
Tobacco consumption
Non-smokers	243 (60.8)	131 (57.7)	1.00 (reference)
Smokers	157 (39.2)	96 (42.3)	1.12	0.73-1.70	0.60
Alcohol consumption
Non-drinkers	218 (54.5)	127 (55.9)	1.00 (reference)
Drinkers	182 (45.5)	100 (44.1)	1.44	0.93-2.24	0.10

¹Odds ratio (OR) adjusted for age, gender, tobacco and alcohol consumption and polymorphisms in the dominant model;

²Significant P values < 0.05.

Table 2 Description of the primers sequences and restriction enzymes for CYP1A1*2A, CYP2E1*5B and CYP2E1*6 polymorphisms analysis

Polymorphisms	Sequence of primers	Restriction Enzyme
Polymorphisms	Sequence of primers	T/t
CYP1A1*2A		MspI
Sense	5’-GA TGA AGA GGT GTA GCC GCT-3’	37 °C/3 h
Antisense	5-TAG GAG TCT TGT CTC ATG CCT-3’
CYP2E1*5B		PstI
Sense	5’-CCA GTC GAG TCT ACA TTG TCA-3’	37 °C/3 h
Antisense	5’-TTC ATT CTG TCT TCT AAC TGG-3’
CYP2E1*6		DraI
Sense	5’-TCG TCA GTT CCT GAA AGC AGG-3’	37 °C/3 h
Antisense	5’-GAG CTC TGA TGC AAG TAT CGC-3’

Table 3 Alleles frequencies of CYP1A1*2A, CYP1A1*2C, CYP2E1*5B, CYP2E1*6, EPHX1 Tyr113His and EPHX1 His139Arg polymorphisms in the sample of this study

Polymorphisms	Allele	Control	Allele frequencies	Case	Allele frequencies
Polymorphisms	Allele	n	Allele frequencies	n	Allele frequencies
CYP1A12A*	T	617	0.77	383	0.84
	C	183	0.23	71	0.16
CYP1A12C*	A	699	0.87	416	0.92
	G	101	0.13	38	0.08
CYP2E15B*	G	751	0.94	381	0.84
	C	49	0.06	73	0.16
CYP2E16*	T	710	0.89	345	0.76
	A	90	0.11	109	0.24
EPHX1 Tyr113His	T	586	0.73	340	0.75
	C	214	0.27	114	0.25
EPHX1 His139Arg	A	615	0.77	373	0.82
	G	185	0.23	81	0.18

Table 4 Association of CYP1A1*2A, CYP1A1*2C, CYP2E1*5B, CYP2E1*6, EPHX1 Tyr113His and EPHX1 His139Arg polymorphisms with sporadic colorectal cancer

Models	Genotype	Control, n (%)	Case, n (%)	OR¹ (95%CI)	P value	Genotype	Control, n (%)	Case, n (%)	OR¹ (95%CI)	P value
	CYP1A1*2A					CYP1A1*2C
Codominant	T/T	246 (61.5)	165 (72.7)	1.00 (reference)		A/A	312 (78)	193 (85)	1.00 (reference)
	T/C	125 (31.3)	53 (23.3)	0.76 (0.49-1.18)	0.27	A/G	75 (18.8)	30 (13.2)	0.70 (0.41-1.20)	0.13
	C/C	29 (7.2)	09 (4)	0.59 (0.25-1.39)		G/G	13 (3.2)	4 (1.8)	0.36 (0.10-1.31)
Dominant	T/T	246 (61.5)	165 (72.7)	1.00 (reference)		A/A	312 (78)	193 (85)	1.00 (reference)
	T/C-C/C	154 (38.5)	62 (27.3)	0.73 (0.49-1.10)	0.13	A/G-G/G	88 (22)	34 (15)	0.64 (0.38-1.06)	0.08
Recessive	T/T-T/C	371 (92.8)	218 (96)	1.00 (reference)		A/A-T/G	387 (96.8)	223 (98.2)	1.00 (reference)
	C/C	29 (7.2)	09 (4)	0.64 (0.27-1.50)	0.29	G/G	13 (3.2)	4 (1.8)	0.38 (0.10-1.38)	0.12
Overdominant	T/T-C/C	275 (68.8)	174 (76.7)	1.00 (reference)		A/A-G/G	325 (81.2)	197 (86.8)	1.00 (reference)
	T/C	125 (31.2)	53 (23.3)	0.80 (0.52-1.23)	0.30	A/G	75 (18.8)	30 (13.2)	0.72 (0.42-1.24)	0.23
Log-additive	T/T	246 (61.5)	165 (72.7)	1.00 (reference)		A/A	312 (78)	193 (85)	1.00 (reference)
	T/C	125 (31.3)	53 (23.3)	0.77 (0.55-1.06)	0.11	A/G	75 (18.8)	30 (13.2)	0.66 (0.43-1.00)	0.05
	C/C	29 (7.2)	09 (4)	0.77 (0.55-1.06)	0.11	G/G	13 (3.2)	4 (1.8)	0.66 (0.43-1.00)	0.05
	CYP2E1*5B					CYP2E1*6
Codominant	G/G	351 (87.8)	157 (69.2)	1.00 (reference)		T/T	314 (78.5)	126 (55.5)	1.00 (reference)
	G/C	49 (12.2)	67 (29.5)	2.66 (1.64-4.32)	< 0.01²	T/A	82 (20.5)	93 (41)	2.81 (1.84-4.28)	< 0.01²
	C/C	0	03 (1.3)	-		A/A	04 (1)	8 (3.5)	7.32 (1.85-28.96)
Dominant	G/G	351 (87.8)	157 (69.2)	1.00 (reference)		T/T	314 (78.5)	126 (55.5)	1.00 (reference)
	G/C-C/C	49 (12.2)	70 (30.8)	2.82 (1.74-4.55)	< 0.00²	T/A-A/A	86 (21.5)	101 (44.5)	2.97 (1.97-4.50)	< 0.01²
Recessive	G/G-G/C	400 (100)	224 (98.7)	1.00 (reference)		T/T-T/A	396 (99)	219 (96.5)	1.00 (reference)
	C/C	0	03 (1.3)	-	-	A/A	4 (1)	8 (3.5)	5.26 (1.35-20.50)	0.016²
Overdominant	G/G-C/C	351 (87.8)	160 (70.5)	1.00 (reference)		T/T-A/A	318 (79.5)	134 (59)	1.00 (reference)
	G/C	49 (12.2)	67 (29.5)	2.58 (1.59-4.19)	< 0.01²	T/A	82 (20.5)	93 (41)	2.64 (1.74-4.01)	< 0.01²
Log-additive	G/G	351 (87.8)	157 (69.2)	1.00 (reference)		T/T	314 (78.5)	126 (55.5)	1.00 (reference)
	G/C	49 (12.2)	67 (29.5)	2.84 (1.78-4.52)	< 0.01²	T/A	82 (20.5)	93 (41)	2.78 (1.91-4.06)	< 0.01²
	C/C	0	03 (1.3)	2.84 (1.78-4.52)	< 0.01²	A/A	4 (1)	8 (3.5)	2.78 (1.91-4.06)	< 0.01²
	EPHX1 Tyr113His					EPHX1 His139Arg
Codominant	T/T	214 (53.5)	126 (55.5)	1.00 (reference)		A/A	235 (58.8)	153 (67.4)	1.00 (reference)
	T/C	158 (39.5)	88 (38.8)	0.95 (0.63-1.41)	0.84	A/G	145 (36.2)	67 (29.5)	0.79 (0.52-1.20)	0.18
	C/C	28 (7)	13 (5.7)	0.80 (0.36-1.76)		G/G	20 (5)	7 (3.1)	0.42 (0.14-1.26)
Dominant	T/T	214 (53.5)	126 (55.5)	1.00 (reference)		A/A	235 (58.8)	153 (67.4)	1.00 (reference)
	T/C-C/C	186 (46.5)	101 (44.5)	0.92 (0.63-1.36)	0.68	A/G-G/G	165 (41.2)	74 (32.6)	0.74 (0.50-1.11)	0.15
Recessive	T/T-T/C	372 (93)	214 (94.3)	1.00 (reference)		A/A-A/G	380 (95)	220 (96.9)	1.00 (reference)
	C/C	28 (7)	13 (5.7)	0.81 (0.37-1.77)	0.60	G/G	20 (5)	7 (3.1)	0.45 (0.15-1.35)	0.14
Overdominant	T/T-C/C	242 (60.5)	139 (61.2)	1.00 (reference)		A/A-G/G	255 (63.8)	160 (70.5)	1.00 (reference)
	T/C	158 (39.5)	88 (38.8)	0.97 (0.65-1.44)	0.88	A/G	145 (36.2)	67 (29.5)	0.83 (0.55-1.25)	0.37
Log-additive	T/T	214 (53.5)	126 (55.5)	1.00 (reference)		A/A	235 (58.8)	153 (67.4)	1.00 (reference)
	T/C	158 (39.5)	88 (38.8)	0.92 (0.67-1.25)	0.59	A/G	145 (36.2)	67 (29.5)	0.74 (0.52-1.04)	0.08
	C/C	28 (7)	13 (5.7)	0.92 (0.67-1.25)	0.59	G/G	20 (5)	7 (3.1)	0.74 (0.52-1.04)	0.08

¹Odds ratio (OR) adjusted for age, gender and tobacco and alcohol consumption and polymorphisms in the dominant model;

²Significant P values < 0.05.

Table 5 Interaction between CYP1A1*2A, CYP1A1*2C, CYP2E1*5B, CYP2E1*6, EPHX1 Tyr113His and EPHX1 His139Arg polymorphisms and tobacco or alcohol consumption on the risk of SCRC

	Tobacco consumption							Alcohol consumption
	Non-smoker			Smoker			P value	Non-drinker			Drinker			P value
	Control	Case	OR¹ (95%CI)	Control	Case	OR¹ (95%CI)	P value	Control	Case	OR¹ (95%CI)	Control	Case	OR¹ (95%CI)	P value
CYP1A1*2A
T/T	156	96	1	90	69	1.12 (0.69-1.83)	0.33	137	92	1	109	73	1.62 (0.97-2.70)	0.35
T/C-C/C	87	35	0.87 (0.51-1.49)	67	27	0.65 (0.35-1.21)		81	35	0.88 (0.50-1.52)	73	27	0.95 (0.50-1.81)
CYP1A1*2C
A/A	190	107	1	122	86	1.08 (0.68-1.69)	0.21	165	105	1	147	88	1.42 (0.89-2.29)	0.91
A/G-G/G	53	24	0.81 (0.43-1.52)	35	10	0.44 (0.18-1.06)		53	22	0.65 (0.34-1.25)	35	12	0.87 (0.38-2.00)
CYP2E1*5B
G/G	215	94	1	136	63	0.90 (0.56-1.44)	0.83	190	85	1	161	72	1.56 (0.96-2.53)	0.68
G/C-C/C	28	37	2.69 (1.41-5.10)	21	33	2.68 (1.33-5.41)		28	42	3.07 (1.63-5.80)	21	28	3.90 (1.82-8.38)
CYP2E1*6
T/T	189	72	1	125	54	0.96 (0.57-1.63)	0.87	171	70	1	143	56	1.47 (0.85-2.55)	0.78
T/A-A/C	54	59	2.89 (1.70-4.93)	32	42	2.99 (1.58-5.64)		47	57	3.14 (1.80-5.48)	39	44	4.10 (2.18-7.72)
EPHX1 Tyr113His
T/T	129	75	1	85	51	0.89 (0.51-1.54)	0.60	122	75	1	92	51	1.30 (0.74-2.31)	0.57
T/C-C/C	114	56	0.84 (0.51-1.40)	72	45	0.92 (0.52-1.62)		96	52	0.83 (0.49-1.41)	90	49	1.36 (0.78-2.37)
EPHX1 His139Arg
A/A	141	89	1	94	64	0.87 (0.52-1.44)	0.38	132	83	1	103	70	1.66 (0.98-2.80)	0.34
A/G-G/G	102	42	0.64 (0.38-1.09)	63	32	0.79 (0.44-1.44)		86	44	0.89 (0.52-1.53)	79	30	1.00 (0.54-1.85)

¹Odds Ratio (OR) adjusted for age, gender and tobacco or alcohol consumption.

Table 6 Comparison between the results of this study and the results of other studies presented in the discussion

Ref.	Country study	Sample size		Gender				Age		Tobacco consumption				Alcohol consumption				Polymorphisms
		Case	Control N	Female		Male		Mean (SD)		Non-smokers		Smokers		Non-drinkers		Drinkers		*CYP1A1*	*CYP2E1*	*EPHX1*
		N	Control N	Case	Control	Case	Control	Case	Control	Case	Control	Case	Control	Case	Control	Case	Control
Huang et al[19], 2005	Bethesda, Maryland	772	777	237	241	535	536	-	-	-	-	-	-	-	-	-	-	-	-	Tyr113His¹, His139Arg¹
van der Logt et al[36], 2006	Netherlands	371	415	159	247	212	168	42	64.0	-	-	-	-	-	-	-	-	-	5B, 6	Tyr113His, His139Arg
Kiss et al[32], 2007	Hungary	500	500	278	278	222	222	64.1	63.8	-	-	-	-	-	-	-	-	-	*5B¹	Tyr113His¹, His139Arg
Yeh et al[42], 2007	China	727	736	317	327	410	409	-	-	-	-	-	-	-	-	-	-	*2C¹	-	-
Yoshida et al[39], 2007	Japan	66	121	26	48	36	73	67.3¹	67.3	35	55	261	61	-	-	-	-	2A, 2C	-	-
Morita et al[33], 2009	Japan	685	778	259	288	426	490	60.2	58.6	-	-	-	-	272	264	413	468	-	*5B	-
Hlavata et al[20], 2010	Czech	495	495	206	230	289	265	57.2¹	55.5	243	195	220	169	-	-	-	-	-	-	Tyr113His, His139Arg
Nisa et al[37], 2010	Japan	685	778	259	288	426	490	-	-	299	326	386	452	-	-	-	-	2A, 2C	-	-
Northwood et al[21], 2010	United Kingdom	317	296	911	122	226	174	62.5	62.0	-	-	-	-	-	-	-	-	*2C	-	Tyr113His, His139Arg
Darazy et al[35], 2011	Lebanon	57	70	-	-	-	-	60.3	62.8	-	-	-	-	-	-	-	-	*2A	*6	-
Jin et al[40], 2011	China	5336	6226	-	-	-	-	-	-	-	-	-	-	-	-	-	-	*2C¹	-	-
Sameer et al[10], 2011	India	86	160	37	72	49	88	52.0	52.0	31	75	55	85	-	-	-	-	-	*5B¹	-
Liu et al[43], 2012	China	6395	7893	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	Tyr113His, His139Arg¹
Silva et al[34], 2012	Brazil	131	206	70	124	61	82	62.4	61.7	-	-	-	-	-	-	-	-	-	*5B¹	-
Zheng et al[41], 2012	China	6673	8102	-	-	-	-	-	-	-	-	-	-	-	-	-	-	2A¹, 2C	-	-
Jiang et al[27], 2013	China	5137	6330	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	5B¹, 6	-
Qian et al[17], 2013	China	4592	5918	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	*6	-
He et al[38], 2014	China	6975	8651	-	-	-	-	-	-	-	-	-	-	-	-	-	-	*2A	-	-
This Study	Brazil	227	400	125	106	2751	121	62.0¹	46.7	243	131	157	96	218	127	182	100	2A, 2C	5B¹, 6¹	Tyr113His, His139Arg

¹P value significant; the variable or polymorphism was associated with SCRC.

Citation: Fernandes GMM, Russo A, Proença MA, Gazola NF, Rodrigues GH, Biselli-Chicote PM, Silva AE, Netinho JG, Pavarino &C, Goloni-Bertollo EM. CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms. World J Gastroenterol 2016; 22(45): 9974-9983
URL: https://www.wjgnet.com/1007-9327/full/v22/i45/9974.htm
DOI: https://dx.doi.org/10.3748/wjg.v22.i45.9974