Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

Table 1 Polymorphisms in the CYP2E1, ALDH2 and ADH1B genes

Locus	Gene	Subunit	Nucleotide	Effect	RFLP
/protein			change
ADH1B	ADH2*1	β1		Wild-type
	ADH2*2	β2	48G>A	His48;
				(earlier as His47)
ALDH2	ALDH2*1			Wild-type
	ALDH2*2		1510G>A	Lys487
CYP2E1	CYP2E1*1A		None	Wild type	Pst I-/Rsa I +
					(c1allele)
	CYP2E1*5B		-1293G>C;		Pst I+/Rsa I -
					(c2 allele)
			-1053C>T

CYP2E1 allele nomenclature, http://www.imm.ki.se; NIAAA publications, http://pubs.niaaa.nih.gov.

Table 2 Primer sequences and lengths of PCR products

Gene	Primer	Size of PCR product (bp)	Chromosomal location
CYP2E1	5’-CCAGTCGAGTCTACATTGTCA-3’	410	10q24.3-qter
	5’-TTCATTCTGTCTTCTAACTGG-3’
ALDH2	5’-CCCTTTGGTGGCTAGAAGATG-3’	91	12q24.2
	5’-CCACACTCACAGTTTTCTCTT-3’
ADH1B	5’-ATTCTGTAGATGGTGGCTGT-3’	76	4q22
	5’-GAAGGGGGGTCACCAGGTTG-3’

Table 3 Alcohol drinking in esophageal cancer cases and control subjects

Alcohol drinking	Cases (n = 80) %	Controls (n = 480) %	P	OR	95% CI
Status
Never	4 (5.0)	132 (27.5)
Former	46 (7.5)	36 (7.5)
Current	20 (87.5)	312 (65.0)	0.17
Dose
Non-drinker	4 (5.0)	132 (27.5)		1
Light	10 (12.5)	153 (31.9)		0.16	0.03-0.24
Moderate	23 (28.7)	117 (24.4)		0.85	0.54-1.07
Heavy	43 (53.8)	78 (16.2)	< 0.0001	3.20	1.32-9.65
Total years of drinking
Never	40 (50.0)	243 (50.6)		1
≤ 30	17 (21.2)	172 (35.8)		0.69	0.36-0.98
> 30	23 (28.8)	65 (13.5)	0.009	1.68	0.96-3.21

Table 4 Genotypes of ALDH2, ADH2 and P4502E1, n (%)

Genotype	Cases	Controls	P	OR	95% CI
	(n = 80)	(n = 480)
ALDH2 genotype
1/1	37 (46.3)	252 (52.5)		1
1/2	43 (53.7)	195 (40.6)	0.094	2.89	1.11-5.64
2/2	0 (0.0)	33 (6.9)
ADH1B genotype
1/1	17 (21.3)	24 (5.0)		1
1/ 2	25 (31.3)	168 (35.0)	< 0.0001	3.67	1.26-8.73
2/2	38 (47.5)	288 (60.0)	< 0.0001	1.46	0.71-2.59
CYP2E1 Pst I/Rsa I
c2/c2	7 (8. 8)	75 (15.6)		1
c1/c2	16 (20.0)	180 (37.5)	0.918
c1/c1	57 (71.3)	225 (46.9)	0.014	2.82	1.23-6.55

Table 5 Probability ratios for the combinations of ALDH2, ADH2 and CYP2E1 genotypes and the amount of alcohol consumed, n (%)

Alcohol drinking	Genotype	Cases (n = 80)	Controls (n = 480)	OR (95% CI)	OR (95% CI)
ALDH2
Never/rare	1/1	7 (8.8)	72 (15.0)	1
-to-light	1/2	7 (8.8)	180 (37.5)	0.56 (0.20-1.59)
	2/2	0 (0.0)	33 (6.9)	0.00 (NC)
Moderate	1/1	30 (37.5)	180 (37.5)	2.29 (0.94-5.57)
-to-heavy	1/2	36 (45.0)	15 (3.1)	8.58 (3.28-22.68)	3.12 (1.86-6.58)
ADH1B
Never/rare	1/2+2/2	13 (16.3)	273 (56.9)	1
-to-light	1/1	1 (1.3)	12 (2.5)	1.00 (0.18-9.22)
Moderate	1/2+2/2	50 (62.5)	183 (38.1)	4.75 (2.53-9.38)
-to-heavy	1/1	16 (20.0)	12 (2.5)	27.12 (8.52-70.19)	5.48 (1.98-14.55)
CYP2E1
Never/rare		5 (6.3)	189 (39.4)	1
-to-light	c1/c1	9 (11.3)	96 (20.0)	0.56 (0.20-1.59)
Moderate	c1/c2+	18 (22.5)	96 (20.0)	1.93 (0.43-2.41)
-to-heavy	c2/c2
	c1/c1	48 (60.0)	99 (20.6)	7.64 (2.82-11.31)	5.32 (1.62-9.28)

Table 6 Probability ratios for the combinations of ADH1B, CYP2E1 and ALDH2 genotypes among moderate-to-heavy drinkers, n (%)

Combined genotypes	Genotype	Cases (n = 80)	Controls (n = 480)	OR	95% CI
ALDH2 + ADH1B	ALDH2*1/1 +ADH1B*1/2 +2/2	28 (35.0)	144 (30.0)	1
	ALDH2*1/2 +	15 (18.8)	27 (1.9)	7.46	3.28-18.32
	ADH1B*1/1
ALDH2 + CYP2E1	ALDH2*1/1 +CYP2E1*c1/c2 +c2/c2	10 (12.5)	60 (12.5)	1
	ALDH2*1/2 +CYP2E1*c1/c1	32 (40.0)	15 (3.1)	6.82	1.44-9.76
ADH1B + CYP2E1	ADH1B*1/2 +2/2 +CYP2E1*c1/c2 +c2/c2	12 (15.0)	36 (2.5)	1
	ADH1B*1/1 +CYP2E1*c1/c1	14 (17.5)	66 (13.8)	6