Interaction of methylenetetrahydrofolate reductase C677T, cytochrome P4502E1 polymorphism and environment factors in esophageal cancer in Kazakh population

Table 1 Environmental risk factors for EC in Kazakh population

Environmental risk factors	Case n (%)	Control, n (%)	P1	OR (95% CI)1
Consumption of green vegetables
Frequently	42 (35.00)	126 (52.50)	-	1.00
Occasionally	45 (37.50)	90 (37.50)	0.106	2.54 (0.91-2.59)
Less	33 (27.50)	24 (10.00)	0.000	4.66 (2.33-9.30)
Consumption of fresh fruits
Frequently	13 (10.83)	1 (29.58)	-	1.00
Occasionally	71 (59.17)	145 (60.42)	0.003	2.79 (1.43-5.43)
Less	36 (30.00)	24 (10.00)	0.000	9.03 (3.90-20.89)
Smoking status
Never	50 (41.67)	100 (41.67)	-	1.00
Former	29 (24.17)	42 (17.50)	0.309	1.39 (0.74-2.62)
Current	41 (34.16)	98 (40.83)	0.509	0.83 (0.47-1.45)
Alcohol drinking frequency
Never	50 (41.67)	152 (63.33)	-	1.00
1-2 times/wk	34 (28.33)	61 (25.42)	0.002	3.28 (1.54-7.01)
3-4 times/wk	29 (24.17)	21 (8.75)	0.000	7.31 (3.14-17.03)
≥ 5 times/wk	7 (5.83)	6 (2.50)	0.005	6.00 (1.71-21.02)
Drinking water source
Safe water	43 (35.83)	163 (67.92)	-	1.00
Shallow well water	20 (16.67)	25 (10.41)	0.002	2.88 (1.47-5.66)
River water	57 (47.50)	52 (21.67)	0.000	4.40 (2.55-7.60)

¹ORs, 95% CIs and P values were calculated in a conditional logistic regression model.

Table 2 Genotype risk assessment of EC in cases and controls

Genotype	Case n (%)	Control n (%)	P1	OR (95% CI)1
MTHFR677
C/C	60 (50.00)	170 (70.83)	-	1.00
C/T	53 (44.17)	59 (24.59)	0.000	2.69 (1.63-4.44)
T/T	7 (5.83)	11 (4.58)	0.144	2.15 (0.77-5.98)
C/C	60 (50.00)	170 (70.83)	-	1.00
C/T + T/T	60 (50.00)	70 (29.17)	0.000	2.62 (1.61-4.28)
CYP2E1 RsaI
C1/C1	94 (78.33)	128 (53.33)	-	1.00
C1/C2	23 (19.17)	90 (37.50)	0.000	0.37 (0.22-0.62)
C2/C2	3 (2.50)	22 (9.17)	0.009	0.19 (0.05-0.66)
C1/C2 + C2/C2	26 (21.67)	112 (46.67)	-	1.00
C1/C1	94 (78.33)	128 (53.33)	0.000	3.00 (1.82-4.96)

¹ORs, 95% CIs and P values were calculated in a conditional logistic regression model.

Table 3 Interaction between MTHFR 677 and consumption of green vegetables, fresh fruits in EC

Consumption of vegetables and fruits	MTHFR 677 genotype	Case (n)	Control (n)	χ2	P	OR (95% CI)
Green vegetables1
Frequently	C/C	19	89	-	-	1.00
Occasionally or less	C/C	41	81	7.62	0.006	2.37 (1.27-4.42)
Frequently	C/T + T/T	23	37	8.85	0.003	2.91 (1.42-5.97)
Occasionally or less	C/T + T/T	37	33	24.50	0.000	5.25 (2.66-10.39)
Freshfruits2
Frequently	C/C	6	54	-	-	1.00
Occasionally or less	C/C	54	116	10.90	0.001	4.19 (1.70-10.34)
Frequently	C/T + T/T	7	17	4.81	0.028	3.71 (1.10-12.54)
Occasionally or less	C/T + T/T	53	53	26.76	0.000	9.00 (3.57-22.71)

SIA: Synergic index of addition; RERI: Relative excess risk of interaction; API: Attributable proportion of interaction. SIA¹ = 5.25/ (2.37 + 2.91 - 1.00) = 1.23, RERI¹ = 5.25 - (2.37 + 2.91) + 1 = 0.97,API¹ = [5.25 - (2.37 + 2.91) + 1]/5.25 = 18.48%; SIA² = 9.00/(4.19 + 3.71 - 1.00) = 1.30, RERI² = 9.00 - (4.19 + 3.71) + 1 = 2.10, API² = [9.00 - (4.19 + 3.71) + 1]/9.00 = 23.33%.

Table 4 Interaction between CYP4502E1 RsaI 677 and alcohol drinking, safety drinking water in EC

		CYP4502E1 rsaI genotype	Case (n)	Control (n)	χ2	P	OR (95% CI)
Alcohol drinking1	Never	C1/C2 + C2/C2	12	70	-	-	1.00
	Yes	C1/C2 + C2/C2	14	42	2.34	0.126	1.94 (0.82-4.60)
	Never	C1/C1	38	82	7.59	0.006	2.70 (1.31-5.57)
	Yes	C1/C1	56	46	31.64	0.000	7.10 (3.44-14.68)
Safe drinking water2	Yes	C1/C2 + C2/C2	9	78	-	-	1.00
	No	C1/C2 + C2/C2	17	34	11.12	0.001	4.33 (1.76-10.69)
	Yes	C1/C1	34	85	10.11	0.001	3.47 (1.56-7.69)
	No	C1/C1	60	43	46.80	0.000	12.09 (5.47-26.74)

SIM: Synergic index of multiplication; SIM1 = 7.10/(1.94 × 2.70) = 1.36, RERI¹ = 7.10 - (1.94 + 2.70) + 1 = 3.46, API¹ = [7.10 - (1.94 + 2.70) + 1]/7.10 = 48.73%; SIA² = 12.09/(4.33 + 3.47 - 1.00) = 1.78, RERI² = 12.09 - (4.33 + 3.47) + 1 = 5.29, API² = [12.09 - (4.33 + 3.47) + 1]/12.09 = 43.76%.

Table 5 Interaction between MTHFR 677 and CYP4502E1 RsaI gene polymorphisms in EC

MTHFR 677 genotype	CYP2E1 rsaI genotype	Case (n)	Control (n)	χ2	P	OR (95% CI)
C/C	C1/C2 + C2/C2	13	82	-	-	1.00
C/T + T/T	C1/C2 + C2/C2	13	30	5.30	0.021	2.73 (1.14-6.56)
C/C	C1/C1	47	88	12.91	0.000	3.37 (1.70-6.68)
C/T + T/T	C1/C1	47	40	33.44	0.000	7.41 (3.60-15.25)

SIA = 7.41/(2.73 + 3.37 - 1.00) = 1.45; RERI = 7.41 - (2.73 + 3.37) + 1 = 2.31; API = [7.41 - (2.73 + 3.37) + 1]/7.41 = 31.17%.