Molecular evaluation of glutathione S transferase family genes in patients with sporadic colorectal cancer

Table 1 Sociodemographic characteristics, risk factors, and polymorphisms GSTT1, GSTM1, GSTP1 A313G in patients with colorectal cancer and controls n (%)

Variables		Case (n = 232)	Control (n = 738)	OR1 (95%CI)
Gender
Male		112 (48)	370 (50)	1.00
Female		120 (52)	368 (50)	2.91 (1.94-4.37)a
Age [yr (mean) ± SD]		(62) ± 12	(48) ± 12
< 62		112 (49)	621 (84)	1.00
≥ 62		120 (51)	117 (16)	8.79 (5.90-13.09)a
Smoking Habit
Non-smoker		130 (56)	465 (63)	1.00
Smoker		102 (44)	273 (37)	1.45 (0.98-2.14)
Alcohol Consumption
Non-drinker		132 (57)	395 (54)	1.00
Drinker		100 (43)	343 (46)	1.28 (0.85-1.91)
GSTP1
Codominant	A/A	227 (43.7)	107 (46.1)	1.00
	A/G	224 (43.2)	102 (44)	1.06 (0.73-1.54)
	G/G	68 (13.1)	23 (9.9)	0.88 (0.48-1.59)
Dominant	A/A	227 (43.7)	107 (46.1)	1.00
	A/G-G/G	292 (56.3)	125 (53.9)	1.02 (0.71-1.45)
Recessive	A/A-A/G	451 (86.9)	209 (90.1)	1
	G/G	68 (13.1)	23 (9.9)	0.85 (0.48-1.50)
Overdominant	A/A-G/G	295 (56.8)	130 (56)	1.00
	A/G	224 (43.2)	102 (44)	1.09 (0.76-1.55)
Additive		-	-	0.97 (0.75-1.27)
GSTT1
	+/+	573 (77.6)	192 (82.8)	1.00
	0/0	165 (22.4)	40 (17.2)	0.65 (0.43-0.98)a
GSTM1
	+/+	385 (52.2)	100 (43.1)	1.00
	0/0	353 (47.8)	132 (56.9)	1.45 (1.06-2.00)a

¹OR adjusted for age, gender, and alcohol and smoking habits and polymorphisms;

^aP < 0.05 vs control. OR: Odds ratio.

Table 2 Interaction between polymorphisms in the genes GSTP1, GSTT1, and GSTM1 and smoking or alcohol habits on the risk of sporadic colorectal cancer

	Tobacco consumption						Alcohol consumption
	Non-smoker			Smoker			Non-smoker			Smoker
	Case	Control	OR1 (95%CI)	Case	Control	OR1 (95%CI)	Case	Control	OR1 (95%CI)	Case	Control	OR1 (95%CI)
GSTP1
A/A	50	136	1.00	57	91	2.33 (1.34-4.05)a	59	116	1.00	48	111	1.31 (0.74-2.31)
A/G-G/G	80	177	1.40 (0.87-2.27)	45	115	1.59 (0.91-2.77)	73	147	1.12 (0.69-1.81)	52	145	1.19 (0.70-2.04)
GSTT1
+/+	110	362	1.00	82	211	1.42 (0.98-2.08)	108	300	1.00	84	273	0.76 (0.52-1.12)
0/0	20	103	0.60 (0.34-1.04)	20	62	1.03 (0.57-1.88)	24	95	0.63 (0.37-1.07)	16	70	0.53 (0.28-1.01)
GSTM1
+/+	52	231	1.00	48	154	1.40 (0.86-2.28)	56	206	1.00	44	179	0.76 (0.46-1.26)
0/0	78	234	1.38 (0.90-2.10)	54	119	2.19 (1.34-3.57)	76	189	1.42 (0.93-2.18)	56	164	1.14 (0.72-1.82)

¹OR adjusted for age, gender, alcohol and smoking habits and polymorphisms;

^aP < 0.05 vs control. OR: Odds ratio.

Table 3 Distribution of the clinical-histopathological parameters in relation to the polymorphisms in the genes GSTP1, GSTT1, and GSTM1 in patients with colorectal cancer n (%)

Models	Genotypes	Tumor progression (TNM) (n = 201)				Primary site
		Non-advanced 61 (31)	Advanced 140 (69)	OR1	95%CI	Colon	Rectum	OR1	95%CI
GSTP1
Codominant	A/A	31 (51)	62 (44)	1.00		42 (46)	65 (46)	1.00
	A/G	23 (38)	65 (47)	1.37	(0.70-2.66)	38 (41)	64 (45)	0.96	(0.54-1.72)
	G/G	6 (10)	11 (8)	1.14	(0.37-3.50)	11 (12)	12 (8)	0.73	(0.29-1.85)
Dominant	A/A	31 (51)	62 (44)	1.00		42 (46)	65 (46)	1.00
	A/G-G/G	29 (48)	76 (55)	1.32	(0.71-2.48)	49 (53)	76 (53)	0.91	(0.53-1.57)
Recessive	A/A-A/G	54 (90)	127 (92)	1.00		80 (87)	129 (91)	1.00
	G/G	6 (10)	11 (8)	1.00	(0.34-2.95)	11 (12)	12 (8)	0.74	(0.31-1.81)
Overdominant	A/A-G/G	37 (61)	73 (52)	1.00		53 (58)	77 (54)	1.00
	A/G	23 (38)	65 (47)	1.34	(0.70-2.56)	38 (41)	64 (45)	1.02	(0.59-1.77)
Aditivo	-	-	-	1.18	(0.73-1.92)	-	-	0.89	(0.59-1.34)
GSTT1
	+/+	47 (78)	47 (78)	1.00		78 (85)	114 (80)	1.00
	0/0	13 (22)	20 (14)	0.57	(0.26-1.27)	13 (14)	27 (19)	1.47	(0.71-3.06)
GSTM1
	+/+	34 (56)	53 (38)	1.00		45 (49.5)	55 (39)	1.00
	0/0	26 (43)	85 (61)	2.33	(1.23-4.41)a	46 (50.5)	86 (61)	1.49	(0.87-2.57)

¹OR adjusted for age, gender, alcohol and smoking habits and polymorphisms;

^aP < 0.05 vs control. OR: Odds ratio.

Table 4 Association between the double combined GSTT1/GSTM genotypes and triple combined GSTT1/GSTM/GSTP1, colorectal cancer, tumor progression, and primary site, adjusted for gender, age, smoking, and alcohol consumption

			Colorectal cancer				Tumor progression (TNM) (n = 198)				Primary site
			Case(n = 198)	Control	OR1	95%CI	Non- advanced (n = 60)	Advanced(n = 138)	OR1	95%CI	Colon(n = 81)	Rectum(n = 117)	OR1	95%CI
Double combination of genotypes				n = 738
GSTT1	GTM1
(+)	(+)		68	303	1.00		26	42	1.00		34	34	1.00
(+)	(-)		97	270	1.50	(1.03-2.19)a	21	76	2.40	(1.19-4.85)a	36	61	1.67	(0.88-3.18)
(-)	(+)		19	82	1.00	(0.55-1.84)	8	11	0.74	(0.26-2.15)	7	12	1.70	(0.59-4.94)
(-)	(-)		14	83	0.61	(0.32-1.19)	5	9	1.20	(0.35-4.10)	4	10	2.60	(0.72-9.46)
Triple combination of genotypes				n = 519
GSTT1	GSTM1	GSTP1
(+)	(+)	Ile/Ile	32	96	1.00		12	20	1.00		16	10	1.00
(+)	(+)	Val*	36	126	1.13	(0.61-2.10)	14	22	0.93	(0.34-2.56)	12	17	1.81	(0.67-4.92)
(-)	(+)	Ile/Ile	10	22	1.45	(0.56-3.77)	5	5	0.50	(0.12-2.18)	18	22	1.41	(0.33-5.98)
(-)	(+)	Val*	9	34	0.90	(0.36-2.25)	3	6	1.07	(0.21-5.31)	2	7	4.57	(0.80-26.24)
(+)	(-)	Ile/Ile	42	86	1.52	(0.81-2.83)	8	22	1.78	(0.65-4.86)	11	19	2.58	(0.99-6.75)
(+)	(-)	Val*	55	98	1.85	(1.01-3.36)a	10	42	2.92	(1.05-8.12)a	19	33	2.06	(0.83-5.15)
(-)	(-)	Ile/Ile	9	23	1.27	(0.48-3.40)	3	5	1.25	(0.25-6.19)	1	7	5.47	(0.92-32.60)
(-)	(-)	Val*	5	34	1.27	(0.11-1.08)	1	3	1.01	(0.14-7.42)	2	2	1.88	(0.27-13.33)

¹OR adjusted for age, gender, alcohol and smoking habits and polymorphisms;

^aP < 0.05 vs control; *Ile/Val ou Val / Ile. OR: Odds Ratio.

Table 5 Polymorphisms GSTT1, GSTM1, and GSTP1 in relation to overall survival of colorectal cancer patients

Polymorphisms	Survival (5 yr)
GSTT1
Positive	64
Negative	68
GSTM1
Positive	67
Negative	63
GSTP1 A313G
AA	61
AG	70
GG	63

^aP < 0.05 vs control.