Methylenetetrahydrofolate Reductase, Diet, and Risk of Colon Cancer

DOI: Published June 1999

Article Figures & Data

Table 1

Associations between MTHFR and colon cancer

MTHFR genotype	Men					Women
MTHFR genotype		Cases (n)	Controls (n)	OR (95% CI)^a	Cases (n)	Controls (n)	OR (95% CI)	Cases (n)	Controls (n)	OR (95% CI)
CC	372	435	1.0	301	392	1.0	673	827	1.0
CT	378	423	1.0 (0.9–1.3)	277	359	1.0 (0.8–1.3)	655	787	1.0 (0.9–1.2)
TT	74	109	0.8 (0.6–1.1)	65	98	0.9 (0.6–1.2)	139	207	0.9 (0.7–1.1)
Distal tumors
CC	175	435	1.0	141	392	1.0	316	827	1.0
CT	189	423	1.1 (0.9–1.5)	130	359	1.0 (0.8–1.3)	329	787	1.1 (0.9–1.3)
TT	41	109	1.0 (0.7–1.5)	32	98	0.9 (0.6–1.5)	73	207	1.0 (0.7–1.3)
Proximal tumors
CC	185	435	1.0	154	392	1.0	339	837	1.0
CT	177	423	1.0 (0.8–1.3)	142	359	1.0 (0.8–1.4)	319	787	1.0 (0.8–1.2)
TT	33	109	0.7 (0.5–1.1)	31	98	0.8 (0.5–1.3)	64	207	0.8 (0.6–1.1)

^a Adjusted for age, BMI, long-term vigorous physical activity, energy intake, dietary fiber, and usual number of cigarettes smoked.

Table 2

Associations between nutrients and MTHFR status in men and women

^a Nutrients were evaluated as nutrients per 1000 kcal and adjusted for sex, age, BMI, long-term vigorous physical activity, usual number of cigarettes smoked per day, total energy intake, and dietary fiber.
^b Cut-off points for men were: folate, 126/197; vitamin B₆, 0.8/1.2; vitamin B₁₂, 1.9/3.31; methionine, 0.74/1.0; alcohol, 1/20. Cut-off points for women were: folate, 141/214; vitamin B₆, 0.85/1.21; vitamin B₁₂, 1.88/3.31; methionine, 0.75/1.0; alcohol, 1/20.
^c Includes any reported use of multivitamin supplements or any supplement that contains folate or B vitamins during the referent year. Low, used no multivitamin supplement; High, used multivitamin supplement.

Table 3

Associations between nutrients and MTHFR status by tumor site

^a Nutrients were evaluated as nutrients per 1000 kcal and adjusted for sex, age, BMI, long-term vigorous physical activity, usual number of cigarettes smoked per day, total energy intake, and dietary fiber.

Table 4

Associations between nutrients and MTHFR status by age at time of diagnosis

^a Nutrients evaluated as nutrients per 1000 kcal and adjusted for sex, age, BMI, long-term vigorous physical activity, usual number of cigarettes smoked per day, total energy intake, and dietary fiber.

Table 5

Combined effects of folate, methionine, and alcohol on risk of colon cancer

Folate^a	Methionine	Allsubjects			Non-alcohol drinkers			Alcohol drinkers
Folate^a	Methionine			CC/CT, OR (95% CI)^b	TT, OR (95% CI)	CC/CT, OR (95% CI)	TT, OR (95% CI)	CC/CT, OR (95% CI)	TT, OR (95% CI)
Low	Low	1.0	1.0 (0.5–2.3)	1.0	0.9 (0.2–4.0)	1.0	1.2 (0.4–3.1)
	Intermediate	0.9 (0.7–1.3)	0.7 (0.4–1.2)	1.0 (0.6–1.6)	1.1 (0.5–2.4)	0.9 (0.6–1.3)	0.4 (0.1–0.9)
	High	1.0 (0.7–1.6)	0.9 (0.2–2.8)	1.1 (0.6–2.1)	0.5 (0.1–2.7)	0.9 (0.5–1.8)	—^c
High	Low	0.9 (0.6–1.4)	0.7 (0.3–1.7)	1.0 (0.5–1.8)	0.7 (0.2–2.3)	0.8 (0.4–1.5)	0.5 (0.1–2.5)
	Intermediate	0.6 (0.4–0.9)	0.6 (0.3–1.0)	0.6 (0.4–1.1)	0.8 (0.3–1.8)	0.6 (0.4–1.1)	0.4 (0.2–1.0)
	High	0.8 (0.5–1.2)	0.3 (0.1–0.9)	0.7 (0.4–1.2)	0.4 (0.1–1.1)	0.9 (0.5–1.7)	—^c

^a High folate was defined as >205 μg per 1000 calories; high methionine was defined as >1.0 g per 1000 calories; low folate was defined as ≤135 μg per 1000 calories; low methionine was defined as <0.75 g per 1000 calories; intermediate levels fell between these values.
^b Nutrients were evaluated as nutrients per 1000 kcal and adjusted for sex, age, BMI, long-term vigorous physical activity, usual number of cigarettes smoked per day, total energy intake, and dietary fiber.
^c Too few numbers in cell to estimate associations.

Table 6

Associations between MTHFR and high- and low-risk diets as determined by combined levels of folate, methionine, and alcohol^a

^a Low risk was defined as folate ≥195 μg per 1000 calories, methionine, ≥1.0 g per 1000 calories and non-alcoholic beverage drinker. High risk was defined as folate ≤140 μg per 1000 calories, methionine ≤0.80 g per 1000 calories, and alcohol >10 g per day. Values between those for low and high are considered intermediate.
^b Nutrients were evaluated as nutrients per 1000 kcal and adjusted for sex and age.