Relationship between genetic polymorphisms of alcohol and aldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males

Table 1 Demographic characteristics among 134 cases and 237 controls

Variables	Cases (%)n = 134	Controls (%)n = 237	Crude OR (95%CI)	P
Age (yr)
Mean±SD	58.9±12.6	57.8±11.8	–	0.41
Education (%)
<High school		107 (76.1)	86 (36.3)	1
High school	23 (17.1)	94 (39.7)	0.20 (0.11–0.34)
>High school	4 (3.0)	57 (24.1)	0.06 (0.06–0.16)	<0.0001
Ethnicity (%)
Mainlander	102 (76.1)	186 (78.5)	1
Fukienese	25 (18.7)	33 (13.9)	1.38 (0.78–2.45)
Others	7 (5.2)	18 (7.6)	0.71 (0.29–1.75)	0.37
Cigarette smoking (%)
No	10 (7.5)	124 (52.3)	1
Yes	124 (92.5)	113 (47.7)	13.61 (6.81–27.21)	<0.0001
Alcohol consumption (%)
No	24 (17.9)	162 (68.4)	1
Yes	110 (82.1)	75 (31.6)	9.9 (5.89–16.64)	<0.0001
Areca chewing (%)
No	66 (49.3)	220 (92.8)	1
Yes	68 (50.8)	17 (7.2)	13.33 (7.33–24.26)	<0.0001

Table 2 Association of ADH2 and ALDH2 genotypes with esophageal cancer risk before and after adjusting for other covariates

Genotypes	Cases (%) n = 134	Controls (%) n = 237	OR (95%CI)	AOR (95%CI)1
ADH2
*2/*2	46 (34.3)	130 (54.9)	1	1
*1/*2	49 (36.6)	91 (38.4)	1.52 (0.94–2.47)	2.28 (1.11–4.68)
*1/*1	39 (29.1)	16 (6.8)	6.89 (3.52–13.49)	7.14 (2.76–18.46)
P for HW2		1.00
ALDH2
*1/*1	32 (23.9)	120 (50.6)	1	1
*1/*2	99 (73.9)	105 (44.3)	3.54 (2.19–5.70)	5.25 (2.47–11.19)
*2/*2	3 (2.2)	12 (5.1)	0.94 (0.25–3.52)	2.44 (0.44–13.55)
P for HW2		0.38

¹Adjusting for age (continuous variable), educational levels (high school vs <high school; >high school vs <high school), cigarette smoking (yes vs no), alcohol consumption (yes vs no), areca chewing (yes vs no), and ADH2 (*1/*1 vs *2/*2 and *1/*2 vs *2/*2) or ALDH2 (*2/*2 vs *1/*1 and *1/*2 vs *1/*1). 2P value for deviation from Hardy–Weinberg equilibrium.

Table 3 Joint effect of ADH2 and ALDH2 genotypes on esophageal cancer risk

ADH2	ALDH2	Cases (%) n = 134	Controls (%) n = 237	OR (95%CI)	AOR (95%CI)1
*1/*2 or *2/*2	*1/*1	23 (17.2)	112 (47.3)	1	1
*1/*1		9 (6.7)	8 (3.4)	4.20 (1.49–11.81)	3.54 (0.93–13.53)
*1/*2 or *2/*2	*1/*2	69 (51.5)	98 (41.4)	2.63 (1.58–4.37)	4.81 (2.17–10.70)
*1/*1		30 (22.4)	7 (3.0)	16.00 (6.40–39.99)	36.79 (9.36–144.65)
*1/*2 or *2/*2	*2/*2	3 (2.2)	11 (4.6)	1.02 (0.27–3.88)	3.40 (0.63–18.33)
*1/*1		0	1 (0.4)	–	–

¹Adjusting for variables in Table 2.

Table 4 Interactive effect between lifetime alcohol consumption and ADH2 and ALDH2 genotypes on esophageal cancer risk

ADH2	ALDH2	Alcohol consumption (g/yr)	Cases (%) n = 134	Controls (%) n = 237	OR (95%CI)	AOR (95%CI)1
*1/*2 or *2/*2	*1/*1	Non-drinker	3 (2.2)	66 (27.9)	1	1
		≤1 500	5 (3.7)	19 (8.0)	5.79 (1.27-26.46)	3.76 (0.65-21.69)
		>1 500	15 (11.2)	27 (11.4)	12.22 (3.27-45.66)	6.07 (1.46-25.26)
*1/*1	*1/*1	Non-drinker	0	2 (0.8)	–	–
		≤1 500	4 (3.0)	4 (1.7)	22.00 (3.62-133.81)	14.91 (1.92-115.95)
		>1 500	5 (3.7)	2 (0.8)	55.00 (7.39-409.22)	33.54 (3.52-319.89)
*1/*2 or *2/*2	*1/*2	Non-drinker	13 (9.7)	76 (32.1)	3.76 (1.03-13.78)	2.92 (0.73-11.63)
		≤1 500	31 (23.1)	15 (6.3)	45.47 (12.26-168.68)	26.67 (6.05-117.57)
		>1 500	25 (18.7)	7 (3.0)	78.57 (18.83-327.89)	39.26 (7.05-218.68)
*1/*1	*1/*2	Non-drinker	5 (3.7)	6 (2.5)	18.33 (3.50-96.18)	18.60 (2.69-128.77)
		≤1 500	14 (10.5)	1 (0.4)	308 (29.80-3 183.05)	139.35 (10.05-∞)
		>1 500	11 (8.2)	0	–	–
*1/*2 or *2/*2	*2/*2	Non-drinker	3 (2.2)	11 (4.6)	6 (1.07-33.60)	2.20 (0.33-14.47)
		≤1 500	0	0	–	–
		>1 500	0	0	–	–
*1/*1	*2/*2	Non-drinker	0	1 (0.4)	–	–
		≤1 500	0	0	–	–
		>1 500	0	0	–	–

¹Adjusting for age, educational levels, cigarette smoking, and areca chewing in Table 2.

Table 5 Allele frequencies of ADH2 and ALDH2 genotypes among different racial groups

Populations	ADH2		ALDH2
	n	*1/*2 (%)	n	*1/*2 (%)
Germans1	233	0.96/0.04	193	1/0
Indians1	167	0.90/0.10	179	0.98/0.02
Chinese1	86	0.32/0.68	132	0.84/0.16
Japanese2	461	0.07/0.93	461	0.58/0.42
Taiwanese3	47	0.27/0.73	47	0.70/0.30
Our study	237	0.26/0.74	237	0.73/0.27

¹Data from Goedde et al[27].

²Data from Higuchi et al[28].

³Data from Thomasson et al [25].