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

Table 4 Associations between serum folate/vitamin B₁₂ concentrations and tumor methylation in relation to the clinical-biological characteristics of patients

Variables	n(%)	Folate (ng/mL) mean (range)	P1	High folate/Low folate2n (%)	P3	Vit.B12 (pg/mL) mean (range)	P1	High B12/Low B122n (%)	P3
Controls (81)		6.3 (3.8-12)	0.14	49 (60.5)/32(39.5)	0.64	312.8 (108-995)	0.14	40 (49.4)/41 (50.6)	0.94
Total cases (86)		5.9 (2.1-12)		48 (55.8)/38(44.2)		269 (50-681)		44 (51.2)/42 (48.8)
Unmethylated	66 (76.7)	5.7 (2.4-12)		32 (48.5)/34 (51.5)		255.2 (79-681)		29 (43.9)/37 (56.1)
Methyalated	20 (23.3)	6.4 (2.1-10)	0.06	16 (80)/4 (20)	0.02	314.7 (50-571)	0.1	15 (75)/5 (25)	0.02
Sex
Male (55)		5.9 (2.4-12)		29 (52.7)/26 (47.3)		274.2 (67-681)		28 (50.9)/27(49.1)
Unmethylated	43 (78.2)	5.8 (2.4-12)		19 (44.2)/24 (55.8)		325.5 (67-571)		18 (41.9)/25 (58.1)
Methylated	12 (21.8)	6.5 (3.9-9.5)	0.1	10 (83.3)/2 (16.7)	0.02	254.4 (83-681)	0.04	10 (83.3)/2 (16.7)	0.02
Female (31)		5.7 (2.1-10)	0.65	19 (61.3)/12 (38.7)	0.55	259.7 (50-523)	0.75	16(51.6)/15 (48.4)	1.005
Unmethylated	23 (74.2)	5.6 (3-8)		13 (56.5)/10 (43.5)		260. 3 (79-521)		11 (47.8)/12 (52.2)
Methylated	8 (25.8)	6.2 (2.1-10)	0.4	6 (75)/2 (25)	0.4	257.8 (50-523)	0.9	5 (62.5)/3 (37.5)	0.7
Age
< 60 yr (36)		5.4 (2.1-8)		18 (50)/18 (50)		238.1(50-571)		14 (38.9)/22(61.1)
Unmethylated	30 (83.3)	5.4 (3-8)		14 (46.7)/16 (53.3)		229.8 (79-465)		11 (36.7)/19 (63.3)
Methylated	6 (16.7)	5.5 (2.1-7.9)	0.5	4 (66.6)/2 (33.3)	0.7	279.5 (50-571)	0.8	3 (50)/3 (50)	0.7
≥ 60 yr (50)		6.3 (2.4-12)	0.045	30 (60)/20 (40)	0.45	291.3 (67-681)	0.15	30 (60)/20(40)	0.15
Unmethylated	36 (72)	6.1 (2.4-12)		18 (50)/18 (50)		276.3 (83-681)		18 (50)/18 (50)
Methylated	14 (28)	6.8 (3.9-10)	0.1	12 (85.7)/2 (14.3)	0.03	329.7 (67-543)	0.1	12 (85.7)/2 (14.3)	0.03
Site
Distal (62)		5.8 (2.4-12)		32 (51.6)/30 (48.4)		260.6 (79-681)		28 (45.2)/34 (54.8)
Unmethylated	61 (98.4)	5.8 (2.4-12)		31 (50.8)/30 (49.2)		255.5 (79-681)		27 (44.3)/34 (55.7)
Methylated	1 (1.6)	7.9	0.3	1 (100)/0 (0)	ND	271 (271)	0.1	1 (100)/0 (0)	ND
Proximal (24)		6.1 (2.1-10)	0.45	16 (66.7)/8 (33.3)	0.25	290.7 (50-543)	0.55	16 (66.7)/8 (33.3)	0.15
Unmethylated	5 (20.8)	5.3 (4.5-6.4)		1 (20)/4 (80)		251 (109-483)		2 (40)/3 (60)
Methylated	19 (79.2)	6.3 (2.1-10)	0.06	15 (78.9)/4 (21.1)	0.03	301.2 (50-543)	0.5	14 (73.7)/5 (26.3)	0.3

¹P-value from Mann-Whitney and t-test where appropriate;

²Median was taken as cut off point for low and high categorical value for serum folate/vitamin B₁₂ levels (5.5 ng/mL, and 240 pg/mL, respectively);

³P value from Fisher's exact test;

⁴Case/control comparison;

⁵Subgroups comparison, cases only. ND:Not determined.