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

Table 5 Combined effects of MTHFR 677 genotype and serum folate/vitamin B₁₂ concentrations on risk of tumor methylation (case-case comparison)

MTHFR 677genotype	n(%)	Folate (ng/mL) mean (range)	P1	High folate/Low folate2n (%)	P3	Vit. B12 (pg/mL) mean (range)	P1	High B12/Low B122n (%)	P3
Cases (86)
CC (42)		5.8 (2.1-8.8)		25 (59.5)/17 (40.5)		254.6 ( 50-673)		20 (47.6)/22 (52.4)
Unmethylated	34 (81)	5.9 (3.4-8.8)		20 (58.8)/14 (41.2)		267.3 (107-673)		16 (47.5)/18 (53.9)
Methylated	8 (19)	5.4 (2.1-7.8)	0.6	5 (62.5)/3 (37.5)	1.00	200.9 (50-429)	0.2	4 (50)/4 (50)	1.00
CT (38)		6.3 (3-12)	0.55	22 (57.9)/16 (42.1)	1.00	296 (79-681)	0.45	21 (55.3)/17 (44.7)	0.5
Unmethylated	27 (71.1)	5.9 (3-12)		12 (44.4)/15 (55.6)		254.1 (79-681)		11 (40.7)/16 (53.9)
Methylated	11 (28.9)	7.2 (5.3-10)	0.06	10 (90.9)/1 (9.1)	0.01	398.7 (150-571)	0.007	10 (90.9)/1 (9.1)	0.01
TT (6)4		4.2 (2.4-5.9)	0.035	1 (16.7)/5 (83.3)	0.08	198.5 (83-300)	0.45	3 (50)/3(50)	1.00
Unmethylated	5 (83.3)	3.8 (2.4-5.1)		0/5 (100)		178.2 (83-258)		2 (40)/3 (60)
Methylated	1 (16.7)	5.9		1 (100)/0		300		1 (100)/0
CT + TT (44)		5.9 (2.4-12)	0.95	23 (52.3)/21 (47.7)	0.5	282.7 (79-681)	0.55	24 (54.5)/20 (45.5)	0.7
Unmethylated	32 (72.7)	5.6 (2.4-12)		12 (37.5)/20 (62.5)		242.3 (79-681)		13 (40.6)/19 (59.4)
Methylated	12 (27.3)	7.1 (5.3-10)	0.002	11(91.7)/1 (8.3)	0.002	390.5 (150-571)	0.002	11 (91.7)/1 (8.3)	0.003

¹P-values for methylated and unmethylated cases, and genotype comparison, Mann-Whitney, t-test and Kruskal Wallis 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;

⁴Since we did not have enough TT cases, the association of serum methyl donors and tumor methylation was not determined in these individuals;

⁵Comparison with the CC genotype, cases only.