Effects of dietary intake and genetic factors on hypermethylation of the hMLH1 gene promoter in gastric cancer

Table 1 Gender and age distribution of cases and controls

	Cases	Controls
Gender
Male	70	140
Female	40	80
Age (yr)
– 39	6	12
40 – 49	11	22
50 – 59	34	68
60 – 69	40	80
70 –	19	38

Table 2 Interaction between cigarette smoking and alcohol intake, and hMLH1 gene promoter hypermethylation in gastric cancer

	Controls	Cases without	Cases with	χ2trend
	(n)	hMLH1 promoter	hMLH1 promoter
		hypermethylation	hypermethylation
		(n)	(n)
Smoking history
Non-smoker	102	27	13	3.827
Smoker	117	42	24
Odds ratio	Referent (1.00)	1.16 (0.62 – 2.17)	3.04a (1.29 – 7.19)
Alcohol drinking
Never	95	26	15	1.327
Ever	124	43	22
Odds ratio	Referent (1.00)	1.07 (0.57 – 2.01)	2.11 (0.90 – 4.98)

Odds ratio was adjusted for age and sex.

^aP<0.05 vs others.

Table 3 Interaction between amount of cigarette smoking and alco-hol intake, and hMLH1 gene promoter hypermethylation in gastric cancer

	OR1 (95%CI2)
	Cases without	Cases with
	hMLH1 promoter	hMLH1 promoter
	hypermethylation	hypermethylation
	vs controls	vs controls
Cumulative smoking
0	1	1
1 – 15	0.96 (0.38 – 2.41)	0.86 (0.22 – 3.41)
16 – 34	0.92 (0.44 – 1.93)	0.75 (0.24 – 2.38)
35 –	0.39a (0.16 – 0.93)	3.17a (1.20 – 8.42)
χ2trend	1.202	6.344a
Ethanol uptake
per week (g/wk)
0	1	1
≤ 280	0.58 (0.29 – 1.14)	1.35 (0.51 – 3.55)
≥ 281	0.68 (0.30 – 1.53)	3.94a (1.21 – 12.80)
χ2trend	0.83	5.419a

¹Odds ratio estimated using a conditional logistic analysis.

²Confidence interval.

^aP < 0.05 vs others.

Table 4 Distribution of controls and cases with or without promoter hypermethylation of the hMLH1 gene according to their intake of food groups which were statistically significant

	Controls	Cases without	Cases with
	(n)	hMLH1 promoter	hMLH1 promoter
		hypermethylation	hypermethylation
		(n)	(n)
Cereal
Low	110	45	17
High	109	24	20
Odds ratio	Referent (1.00)	0.56a (0.32 – 0.99)	0.94 (0.45 – 1.96)
Potato
Low	109	36	27
High	110	33	10
Odds ratio	Referent (1.00)	1.00 (0.57 – 1.74)	0.30b (0.14 – 0.67)
Vegetable
Low	110	29	12
High	109	40	25
Odds ratio	Referent (1.00)	1.42 (0.82 – 2.46)	2.17a (1.03 – 4.58)
Mushroom
Low	110	26	18
High	109	43	19
Odds ratio	Referent (1.00)	1.85a (1.05 – 3.27)	0.89 (0.43 – 1.83)
Fruit
Low	110	25	13
High	109	44	24
Odds ratio	Referent (1.00)	1.86a (1.06 – 3.27)	1.69 (0.81 – 3.54)
Butter, cheese,
and margarine
Low	110	49	24
High	109	20	13
Odds ratio	Referent (1.00)	0.45b (0.24 – 0.81)	0.44a (0.20 – 0.93)

Odds ratio was adjusted for age and sex.

^aP < 0.05.

^bP < 0.01 vs others.

Table 5 Distribution of controls and cases with or without promoter hypermethylation of the hMLH1 gene according to their intake of nutrients, vitamins, and minerals which were statistically significant

	Controls	Cases without	Cases with
	(n)	hMLH1 promoter	hMLH1 promoter
		hypermethylation	hypermethylation
		(n)	(n)
Protein
Low	109	25	18
High	110	44	19
Odds ratio	Referent (1.00)	1.81a (1.03 – 3.17)	1.00 (0.49 – 2.02)
Phosphorus
Low	109	25	20
High	110	44	17
Odds ratio	Referent (1.00)	1.82a (1.03 – 3.19)	0.77 (0.38 – 1.57)
Potassium
Low	109	22	15
High	110	47	22
Odds ratio	Referent (1.00)	2.38b (1.32 – 4.26)	1.24 (0.60 – 2.56)
Vitamin C
Low	110	19	13
High	109	50	24
Odds ratio	Referent (1.00)	2.78b (1.53 – 5.05)	1.74 (0.84 – 3.63)
Zinc
Low	110	23	15
High	109	46	22
Odds ratio	Referent (1.00)	2.20b (1.23 – 3.91)	1.31 (0.64 – 2.70)
Calcium
Low	110	22	15
High	109	47	22
Odds ratio	Referent (1.00)	2.32b (1.30 – 4.14)	1.34 (0.65 – 2.76)

Odds ratio was adjusted for age and sex.

^aP < 0.05,

^bP < 0.01 vs others.

Table 6 Distribution of controls and cases with or without promoter hypermethylation of the hMLH1 gene according to the genetic poly-morphisms of GSTM1, GSTT1, CYP1A1, CYP2E1, NAT2, ALDH2, and L-myc

	Controls	Cases without	Cases with
	(n)	hMLH1 promoter	hMLH1 promoter
		hypermethylation	hypermethylation
		(n)	(n)
GSTM1
Undeleted	90	21	13
Deleted	130	48	25
Odds ratio	Referent (1.00)	1.67 (0.93 – 3.00)	1.18 (0.56 – 2.47)
GSTT1
Undeleted	117	32	17
Deleted	103	37	21
Odds ratio	Referent (1.00)	1.32 (0.76 – 2.29)	1.47 (0.72 – 2.98)
CYP1A1
Ile/Ile	115	36	22
Ile/Val+Val/Val	104	33	15
Odds ratio	Referent (1.00)	1.02 (0.59 – 1.77)	0.74 (0.36 – 1.52)
CYP2E1
c1/c1	129	44	25
c1/c2+c2/c2	88	26	13
Odds ratio	Referent (1.00)	0.89 (0.51 – 1.56)	0.76 (0.37 – 1.59)
ALDH2
NN	139	38	26
ND+DD	79	31	11
Odds ratio	Referent (1.00)	1.45 (0.83 – 2.52)	0.73 (0.34 – 1.56)
L-myc
Low	52	20	9
High	164	48	29
Odds ratio	Referent (1.00)	1.59 (0.86 – 2.92)	1.56 (0.61 – 3.99)

Odds ratio was adjusted for age and sex.

Table 7 Frequencies of mutations of the p53 and Ki-ras genes, and microsatellite instability according to hMLH1 promoter hypermethylation

Gene	hMLH1 promoter hypermethylation		OR1 (95%CI2)	χ2	P
	Yes (%)	No (%)
P53
No	31 (81.58)	46 (65.71)	1.00	4.199	0.041
Yes	7 (18.42)	24 (34.29)	0.34 (0.12 – 0.95)
Ki-ras
No	37 (97.37)	58 (93.55)	1.00	0.407	0.524
Yes	1 (2.63)	4 (6.45)	0.47 (0.05 – 4.72)
3MSI
No	28 (73.68)	66 (92.86)	1.00	7.458	0.006
Yes	10 (26.32)	4 (7.14)	6.19 (1.67 – 22.88)

¹Odds ratio was adjusted for age and sex.

²Confidence interval.

³Microsatellite instability.