CYP1A1, GSTM1, GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men

doi:10.3748/wjg.v19.i25.4023

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jul 7, 2013; 19(25): 4023-4030
Published online Jul 7, 2013. doi: 10.3748/wjg.v19.i25.4023

Table 1 Selected characteristics of the study subjects

Characteristics	Cases	Controls
	(n = 455)	(n = 1052)
Age (yr), mean ± SD	52.4 ± 0.8	52.4 ± 0.9
Body mass index (kg/m²), mean ± SD	24.1 ± 2.8	23.7 ± 2.5
MET-h/wk, median (IQR)¹	12 (3-24)	14 (5-24)
Smoking (cigarette-yr)
0	20.90%	33.70%
1-399	14.10%	18.80%
400-799	45.50%	33.70%
≥ 800	19.60%	13.70%
Alcohol use (mL/d)
Never	11.20%	13.80%
Past	2.90%	3.10%
< 30	21.10%	30.70%
30-59	34.10%	28.70%
≥ 60	30.80%	23.70%

¹Leisure-time physical activity. IQR: Interquartile range; MET: Metabolic equivalent.

Table 2 Associations between genetic polymorphisms and colorectal adenomas n (%)

Genotype	Cases	Controls	Crude	Adjusted³
			OR (95%CI)
CYP1A12A*
0¹	174 (38.2)	388 (36.9)	1.00 (referent)	1.00 (referent)
1	219 (48.1)	508 (48.3)	0.96 (0.76-1.22)	0.97 (0.76-1.24)
2	62 (13.6)	156 (14.8)	0.89 (0.63-1.25)	0.86 (0.60-1.23)
CYP1A12C*
0¹	281 (61.8)	611 (58.1)	1.00 (referent)	1.00 (referent)
1	152 (33.4)	389 (37.0)	0.85 (0.67-1.07)	0.81 (0.64-1.03)
2	22 (4.8)	52 (4.9)	0.92 (0.55-1.54)	0.94 (0.55-1.60)
GSTM1
Non-null	200 (44.0)	506 (48.1)	1.00 (referent)	1.00 (referent)
Null	255 (56.0)	546 (51.9)	1.18 (0.95-1.47)	1.19 (0.94-1.49)
GSTT1
Non-null	258 (56.7)	552 (52.5)	1.00 (referent)	1.00 (referent)
Null	197 (43.3)	500 (47.5)	0.84 (0.68-1.05)	0.87 (0.70-1.10)
GSTM1 + GSTT1
0²	118 (25.9)	273 (26.0)	1.00 (referent)	1.00 (referent)
1	222 (48.8)	512 (48.7)	1.00 (0.77-1.31)	1.04 (0.79-1.37)
2 (both null)	115 (25.3)	267 (25.4)	1.00 (0.73-1.35)	1.04 (0.76-1.42)
NQO1 C609T
CC	161 (35.4)	412 (39.2)	1.00 (referent)	1.00 (referent)
CT	220 (48.4)	489 (46.5)	1.15 (0.90-1.47)	1.18 (0.92-1.52)
TT	74 (16.3)	151 (14.4)	1.25 (0.90-1.75)	1.31 (0.93-1.84)

¹Number of variant alleles;

²Number of null genotypes;

³Adjusted for age, hospital, rank in the Self-Defense Forces, body mass index, cigarette smoking, alcohol use, leisure-time physical activity and parental history of colorectal cancer.

Table 3 Associations between combinations of genetic polymorphisms and colorectal adenomas

Genotype 1	Genotype 2	n¹	OR (95%CI)²	Interaction (P)
CYP1A12A*	GSTM1			0.94
0³	Non-null	75/182	1.00 (referent)
0	Null	99/206	1.20 (0.83-1.74)
≥ 1	Non-null	125/324	0.96 (0.67-1.35)
≥ 1	Null	156/340	1.12 (0.80-1.58)
CYP1A12A*	GSTT1			0.08
0³	Non-null	92/210	1.00 (referent)
0	Null	82/178	1.14 (0.79-1.65)
≥ 1	Non-null	166/342	1.15 (0.83-1.58)
≥ 1	Null	115/322	0.85 (0.61-1.19)
CYP1A12A*	GSTM1 + GSTT1			0.44
0³	0⁴	41/102	1.00 (referent)
0	1	85/188	1.19 (0.75-1.88)
0	2 (both null)	48/98	1.35 (0.81-2.27)
≥ 1	0	77/171	1.17 (0.74-1.86)
≥ 1	1	137/324	1.12 (0.73-1.72)
≥ 1	2 (both null)	67/169	1.03 (0.64-1.66)
CYP1A12A*	NQO1 C609T			0.09
0³	CC	63/133	1.00 (referent)
0	CT + TT	111/255	0.92 (0.63-1.36)
≥ 1	CC	98/279	0.73 (0.49-1.07)
≥ 1	CT + TT	183/385	1.02 (0.71-1.47)
CYP1A12C*	GSTM1			0.77
0³	Non-null	127/294	1.00 (referent)
0	Null	154/317	1.16 (0.86-1.55)
≥ 1	Non-null	73/212	0.79 (0.56-1.12)
≥ 1	Null	101/229	0.98 (0.71-1.36)
CYP1A12C*	GSTT1			0.24
0³	Non-null	154/321	1.00 (referent)
0	Null	127/290	0.97 (0.73-1.31)
≥ 1	Non-null	104/231	0.93 (0.68-1.27)
≥ 1	Null	70/210	0.69 (0.49-0.97)
CYP1A12C*	GSTM1 + GSTT1			0.37
0³	4	74/156	1.00 (referent)
0	1	133/303	0.96 (0.67-1.37)
0	2 (both null)	74/152	1.13 (0.75-1.69)
≥ 1	0	44/117	0.79 (0.50-1.25)
≥ 1	1	89/209	0.92 (0.63-1.35)
≥ 1	2 (both null)	41/115	0.72 (0.45-1.15)
CYP1A12C*	NQO1 C609T			0.05
0³	CC	102/220	1.00 (referent)
0	CT + TT	179/391	0.99 (0.73-1.34)
≥ 1	CC	59/192	0.61 (0.42-0.91)
≥ 1	CT + TT	115/249	0.98 (0.71-1.37)

¹Number of cases/controls;

²Adjusted for age, hospital, rank in the Self-Defense Forces, body mass index, cigarette smoking, alcohol use, leisure-time physical activity and parental history of colorectal cancer;

³Number of variant alleles;

⁴Number of null genotypes.

Table 4 Associations between genetic polymorphisms and colorectal adenomas with stratification by smoking category

Genotype	< 20 pack-years		≥20 pack-years		Interaction (P)
	n¹	OR (95%CI)²	n¹	OR (95%CI)²
CYP1A12A*
0³	59/207	1.00 (referent)	115/181	2.22 (1.52-3.24)	0.45
≥ 1	100/346	1.05 (0.73-1.53)	181/318	1.95 (1.37-2.76)
CYP1A12C*
0³	106/329	1.00 (referent)	175/282	1.90 (1.41-2.56)	0.59
≥ 1	53/224	0.76 (0.52-1.11)	121/217	1.65 (1.20-2.27)
GSTM1
Non-null	69/264	1.00 (referent)	131/242	1.99 (1.41-2.82)	0.96
Null	90/289	1.19 (0.83-1.71)	165/257	2.35 (1.68-3.29)
GSTT1
Non-null	89/268	1.00 (referent)	169/284	1.74 (1.27-2.38)	0.26
Null	70/285	0.74 (0.52-1.06)	127/215	1.69 (1.21-2.36)
GSTM1 + GSTT1
0⁴	39/134	1.00 (referent)	79/139	1.87 (1.18-2.96)	0.63
1	80/264	1.03 (0.67-1.61)	142/248	1.91 (1.26-2.91)
2 (both null)	40/155	0.89 (0.54-1.48)	75/112	2.14 (1.34-3.43)
NQO1 C609T
CC	52/221	1.00 (referent)	109/191	2.23 (1.51-3.29)	0.46
CT + TT	107/332	1.35 (0.93-1.97)	187/308	2.51 (1.75-3.60)

¹Number of cases/controls;

²Adjusted for age, hospital, rank in the Self-Defense Forces, body mass index, cigarette smoking, alcohol use, leisure-time physical activity and parental history of colorectal cancer;

³Number of variant alleles;

⁴Number of null genotypes.

Table 5 Associations between combinations of genetic polymorphisms and colorectal adenomas with stratification by smoking category

Genotype 1	Genotype 2	< 20 pack-years		≥20 pack-years		Interaction (P)
		n¹	OR (95%CI)²	n¹	OR (95%CI)²
CYP1A12A*	GSTM1					0.44
0³	Non-null	25/87	1.00 (referent)	50/95	1.78 (1.00-3.14)
0	Null	34/120	0.94 (0.52-1.69)	65/86	2.53 (1.45-4.43)
≥ 1	Non-null	44/177	0.86 (0.49-1.50)	81/147	1.82 (1.07-3.10)
≥ 1	Null	56/169	1.19 (0.69-2.05)	100/171	1.92 (1.14-3.22)
CYP1A12A*	GSTT1					0.56
0³	Non-null	29/98	1.00 (referent)	63/112	1.94 (1.15-3.28)
0	Null	30/109	0.95 (0.53-1.71)	52/69	2.53 (1.44-4.44)
≥ 1	Non-null	60/170	1.26 (0.75-2.11)	106/172	2.07 (1.27-3.39)
≥ 1	Null	40/176	0.81 (0.47-1.40)	75/146	1.70 (1.02-2.82)
CYP1A12A*	GSTM1 + GSTT1					0.40
0³	0⁴	14/42	1.00 (referent)	27/60	1.34 (0.62-2.89)
0	1	26/101	0.76 (0.36-1.62)	59/87	2.02 (1.00-4.07)
0	2 (both null)	19/64	0.87 (0.39-1.94)	29/34	2.46 (1.11-5.46)
≥ 1	0	25/92	0.83 (0.39-1.78)	52/79	1.89 (0.93-3.86)
≥ 1	1	54/163	1.01 (0.51-2.01)	83/161	1.52 (0.78-2.98)
≥ 1	2 (both null)	21/91	0.73 (0.33-1.59)	46/78	1.66 (0.81-3.40)
CYP1A12A*	NQO1 C609T					0.76
0³	CC	20/73	1.00 (referent)	43/60	2.55 (1.34-4.86)
0	CT + TT	39/134	1.04 (0.56-1.94)	72/121	2.15 (1.20-3.86)
≥ 1	CC	32/148	0.81 (0.43-1.54)	66/131	1.69 (0.94-3.04)
≥ 1	CT + TT	68/198	1.29 (0.72-2.29)	115/187	2.23 (1.28-3.89)
CYP1A12C*	GSTM1					0.78
0²	Non-null	47/150	1.00 (referent)	80/144	1.74 (1.13-2.69)
0	Null	59/179	1.04 (0.67-1.63)	95/138	2.15 (1.40-3.31)
≥ 1	Non-null	22/114	0.63 (0.36-1.11)	51/98	1.59 (0.98-2.57)
≥ 1	Null	31/110	0.94 (0.55-1.58)	70/119	1.77 (1.13-2.78)
CYP1A12C*	GSTT1					0.11
0²	Non-null	60/151	1.00 (referent)	94/170	1.39 (0.93-2.07)
0	Null	46/178	0.66 (0.42-1.03)	81/112	1.80 (1.18-2.75)
≥ 1	Non-null	29/117	0.65 (0.39-1.09)	75/114	1.62 (1.06-2.48)
≥ 1	Null	24/107	0.59 (0.34-1.01)	46/103	1.06 (0.66-1.69)
CYP1A12C*	GSTM1 + GSTT1					0.22
0²	0⁴	29/71	1.00 (referent)	45/85	1.26 (0.71-2.23)
0	1	49/159	0.73 (0.42-1.26)	84/144	1.41 (0.84-2.37)
0	2 (both null)	28/99	0.69 (0.38-1.28)	46/53	2.03 (1.12-3.69)
≥ 1	0	10/63	0.39 (0.17-0.87)	34/54	1.46 (0.79-2.72)
≥ 1	1	31/105	0.75 (0.41-1.36)	58/104	1.31 (0.76-2.26)
≥ 1	2 (both null)	12/56	0.53 (0.25-1.15)	29/59	1.09 (0.58-2.05)
CYP1A12C*	NQO1 C609T					0.34
0²	CC	34/127	1.00 (referent)	68/93	2.64 (1.60-4.36)
0	CT + TT	72/202	1.33 (0.83-2.12)	107/189	2.10 (1.33-3.31)
≥ 1	CC	18/94	0.75 (0.39-1.41)	41/98	1.41 (0.83-2.41)
≥ 1	CT + TT	35/130	1.03 (0.60-1.77)	80/119	2.47 (1.53-4.00)

¹Number of cases/controls;

²Adjusted for age, hospital, rank in the Self-Defense Forces, body mass index, cigarette smoking, alcohol use, leisure-time physical activity and parental history of colorectal cancer;

³Number of variant alleles;

⁴Number of null genotypes.

Citation: Hamachi T, Tajima O, Uezono K, Tabata S, Abe H, Ohnaka K, Kono S. CYP1A1, GSTM1, GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men. World J Gastroenterol 2013; 19(25): 4023-4030
URL: https://www.wjgnet.com/1007-9327/full/v19/i25/4023.htm
DOI: https://dx.doi.org/10.3748/wjg.v19.i25.4023