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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Methylenetetrahydrofolate Reductase, Diet, and Risk of Colon Cancer

Martha L. Slattery, John D. Potter, Wade Samowitz, Donna Schaffer and Mark Leppert
Martha L. Slattery
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John D. Potter
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Wade Samowitz
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Donna Schaffer
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Mark Leppert
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DOI:  Published June 1999
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Article Figures & Data

Tables

  • Table 1

    Associations between MTHFR and colon cancer

    MTHFR genotypeMenWomenAll subjects
    Cases (n)Controls (n)OR (95% CI)aCases (n)Controls (n)OR (95% CI)Cases (n)Controls (n)OR (95% CI)
    CC 3724351.03013921.06738271.0
    CT 3784231.0 (0.9–1.3)2773591.0 (0.8–1.3)6557871.0 (0.9–1.2)
    TT 741090.8 (0.6–1.1)65980.9 (0.6–1.2)1392070.9 (0.7–1.1)
    Distal tumors
     CC1754351.01413921.03168271.0
     CT1894231.1 (0.9–1.5)1303591.0 (0.8–1.3)3297871.1 (0.9–1.3)
     TT411091.0 (0.7–1.5)32980.9 (0.6–1.5)732071.0 (0.7–1.3)
    Proximal tumors
     CC1854351.01543921.03398371.0
     CT1774231.0 (0.8–1.3)1423591.0 (0.8–1.4)3197871.0 (0.8–1.2)
     TT331090.7 (0.5–1.1)31980.8 (0.5–1.3)642070.8 (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

    MTHFR genotypeOR (95% CI)a
    LowIntermediateHigh
    Folateb
     CC1.00.8 (0.7–1.1)0.8 (0.6–1.2)
     CT1.0 (0.8–1.3)0.9 (0.7–1.2)0.8 (0.6–1.1)
     TT0.8 (0.5–1.3)0.8 (0.6–1.2)0.6 (0.4–1.0)
    Vitamin B6
     CC1.00.8 (0.6–1.0)0.9 (0.7–1.3)
     CT0.9 (0.7–1.2)0.9 (0.7–1.2)0.9 (0.6–1.2)
     TT0.8 (0.5–1.3)0.8 (0.6–1.2)0.6 (0.4–1.0)
    Vitamin B12
     CC1.01.1 (0.8–1.4)1.0 (0.8–1.4)
     CT1.1 (0.7–1.9)1.1 (0.9–1.4)0.9 (0.6–1.2)
     TT1.2 (0.7–1.9)0.9 (0.6–1.2)0.7 (0.5–1.2)
    Methionine
     CC1.00.9 (0.7–1.2)0.8 (0.6–1.0)
     CT1.0 (0.7–1.3)0.9 (0.7–1.2)0.9 (0.6–1.2)
     TT0.9 (0.5–1.4)0.7 (0.5–1.0)0.8 (0.5–1.3)
    Alcohol
     CC1.00.9 (0.7–1.2)0.8 (0.6–1.1)
     CT0.9 (0.7–1.1)1.0 (0.8–1.3)1.2 (0.9–1.6)
     TT1.0 (0.7–1.4)0.5 (0.3–0.8)1.0 (0.6–1.6)
    Multivitamin supplementc
     CC1.01.1 (0.9–1.3)
     CT1.0 (0.8–1.2)1.1 (0.9–1.4)
     TT0.9 (0.7–1.2)0.9 (0.6–1.3)
    • 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

    MTHFR genotypeProximal, OR (95% CI)aDistal, OR (95% CI)
    LowIntermediateHighLowIntermediateHigh
    Folate
     CC1.00.8 (0.6–1.1)0.9 (0.6–1.4)1.00.9 (0.6–1.2)0.8 (0.5–1.2)
     CT0.9 (0.7–1.3)0.9 (0.6–1.2)0.8 (0.6–1.3)1.1 (0.8–1.6)1.0 (0.7–1.3)0.7 (0.5–1.2)
     TT0.7 (0.4–1.3)0.8 (0.5–1.4)0.5 (0.2–0.9)0.9 (0.5–1.5)0.9 (0.5–1.4)0.8 (0.5–1.5)
    Vitamin B6
     CC1.00.8 (0.6–1.1)1.1 (0.7–1.6)1.00.7 (0.5–1.0)0.8 (0.5–1.1)
     CT1.0 (0.7–1.4)0.8 (0.6–1.2)1.0 (0.6–1.4)0.8 (0.6–1.2)0.9 (0.7–1.3)0.8 (0.5–1.2)
     TT0.8 (0.4–1.5)0.8 (0.5–1.3)0.5 (0.3–0.9)0.8 (0.4–1.4)0.8 (0.5–1.3)0.7 (0.4–1.3)
    Vitamin B12
     CC1.01.3 (0.9–1.8)1.2 (0.8–1.8)1.00.8 (0.6–1.2)0.9 (0.6–1.3)
     CT1.3 (0.9–1.8)1.3 (0.9–1.8)1.0 (0.7–1.5)1.0 (0.7–1.5)1.0 (0.7–1.4)0.8 (0.6–1.2)
     TT1.1 (0.6–2.2)1.0 (0.6–1.6)0.6 (0.3–1.3)1.1 (0.6–2.1)0.8 (0.5–1.2)0.9 (0.5–1.6)
    • 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

    MTHFR genotype≤60 years, OR (95% CI)a>60 years, OR (95% CI)
    LowIntermediateHighLowIntermediateHigh
    Folate
     CC1.00.8 (0.5–1.3)0.7 (0.3–1.3)1.00.9 (0.6–1.2)0.9 (0.6–1.4)
     CT1.0 (0.6–1.6)0.7 (0.4–1.1)0.5 (0.3–1.1)1.0 (0.7–1.4)1.0 (0.8–1.4)0.9 (0.6–1.3)
     TT1.1 (0.5–2.7)1.0 (0.4–1.9)0.6 (0.2–1.7)0.7 (0.4–1.2)0.8 (0.5–1.3)0.6 (0.4–1.1)
    Vitamin B6
     CC1.00.7 (0.5–1.2)0.6 (0.3–1.2)1.00.8 (0.6–1.1)1.0 (0.7–1.5)
     CT0.7 (0.5–1.2)0.7 (0.4–1.1)0.8 (0.4–1.7)1.0 (0.7–1.4)1.0 (0.7–1.4)0.9 (0.6–1.3)
     TT0.6 (0.2–1.3)1.0 (0.5–2.0)1.1 (0.4–2.9)0.9 (0.5–1.7)0.8 (0.5–1.2)0.5 (0.3–0.9)
    Vitamin B12
     CC1.00.9 (0.5–1.5)0.9 (0.5–1.5)1.01.1 (0.8–1.5)1.1 (0.7–1.5)
     CT1.0 (0.6–1.8)0.8 (0.5–1.3)0.7 (0.4–1.3)1.2 (0.8–1.7)1.3 (0.9–1.7)0.9 (0.6–1.3)
     TT1.6 (0.6–4.2)0.7 (0.4–1.6)1.0 (0.4–2.6)1.0 (0.5–1.8)0.9 (0.6–1.3)0.6 (0.4–1.2)
    • 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

    FolateaMethionineAllsubjectsNon-alcohol drinkersAlcohol drinkers
    CC/CT, OR (95% CI)bTT, OR (95% CI)CC/CT, OR (95% CI)TT, OR (95% CI)CC/CT, OR (95% CI)TT, OR (95% CI)
    LowLow1.01.0 (0.5–2.3)1.00.9 (0.2–4.0)1.01.2 (0.4–3.1)
    Intermediate0.9 (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)
    High1.0 (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
    HighLow0.9 (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)
    Intermediate0.6 (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)
    High0.8 (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 alcohola

    MTHFR genotypeOR (95% CI)b
    High riskIntermediate riskLow risk
    CC/TT cases/controls109/961180/144939/64
    TT cases/controls11/10121/1797/18
    All subjects
     CC/CT1.00.8 (0.6–1.0)0.6 (0.4–1.0)
     TT1.0 (0.4–2.4)0.7 (0.5–1.0)0.4 (0.1–0.9)
    Subjects ≤60 years
     CC/CT1.00.7 (0.4–1.2)0.6 (0.2–1.9)
     TT0.6 (0.1–2.6)0.8 (0.4–1.7)0.2 (0.02–1.8)
    Subjects ≤60 years
     CC/CT1.00.8 (0.5–1.0)0.6 (0.3–1.0)
     TT1.3 (0.4–4.5)0.6 (0.4–0.9)0.4 (0.2–1.2)
    • 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.

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June 1999
Volume 8, Issue 6
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Methylenetetrahydrofolate Reductase, Diet, and Risk of Colon Cancer
Martha L. Slattery, John D. Potter, Wade Samowitz, Donna Schaffer and Mark Leppert
Cancer Epidemiol Biomarkers Prev June 1 1999 (8) (6) 513-518;

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Methylenetetrahydrofolate Reductase, Diet, and Risk of Colon Cancer
Martha L. Slattery, John D. Potter, Wade Samowitz, Donna Schaffer and Mark Leppert
Cancer Epidemiol Biomarkers Prev June 1 1999 (8) (6) 513-518;
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