Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status

Table 2 Stratification analysis of tumors and genes promoter methylation frequencies

Variables	Methylation positive (%)						Methylated tumors2n (%)	OR (95% CI, P)3
	p16	P1	hMLH1	P1	hMSH2	P1
Sex
Male (90)	13 (14.4)	0.06	10 (11.1)	NS	4 (4.4)	NS	21 (23.3)	1
Female (61)	17 (27.9)		10 (16.4)		0 (0)		23 (37.7)	2.3 (1.1–5.04, 0.03)
Total (151)	30 (19.9)		20 (13.2)		4 (2.6)		44 (29.1)
Age (yr)
< 60 (66)	15 (22.7)	NS	7 (10.6)	NS	0 (0)	NS	19 (28.8)	1
≥ 60 (85)	15 (17.6)		13 (15.3)		4 (4.7)		25 (29.4)	1.1 (0.6–2.4, 0.7)
Tumor site
Proximal (60)	29 (48.3)	0.00	20 (33.3)	0.00	4 (6.7)	0.02	43 (71.7)	1
Distal (91)	1 (1.1)		0 (0)		0 (0)		1 (1.1)	0.002 (0.00–0.023, 0.00)
Serum folate (86)
Low (38)	2 (5.3)	0.04	4 (10.5)	NS	0 (0)	NS	4 (10.5)	1
High (48)	10 (20.8)		10 (20.8)		3 (6.3)		16 (33.3)	4.9 (1.4 -17.7, 0.01)
Serum vitamin B12 (86)
Low (42)	2 (4.8)	0.02	5 (11.9)	NS	0 (0)	NS	5 (11.9)	1
High (44)	10 (22.7)		9 (20.5)		3 (6.8)		15 (34.1)	3.9 (1.1-13.9, 0.03)
MTHFR 677 genotype4
CC (64)	13 (20.3)	NS	7 (10.9)	NS	0 (0)	NS	15 (23.4)	1
CT (80)	17 (21.3)	NS	12 (15)	NS	3 (3.8)	NS	28 (35)	1.92 (0.9-4.2, 0.09)
TT (7)	0 (0)	NS	1 (14.3)	NS	1 (14.3)	NS	1 (14.3)	0.7 (0.07-6.1, 0.7)
CT + TT (87)	17 (19.5)	NS	13 (14.9)	NS	4 (4.6)	NS	29 (33.3)	1.8 (0.8-3.9, 0.125)

¹Fisher's exact test;

²tumors with at least one methylated gene promoter;

³the first category was taken as reference. Odds ratio adjusted for age, sex, and smoking status;

⁴For genotype comparison CC used as the reference category. NS: Not significant.