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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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A Polymorphism of the Methionine Synthase Gene: Association with Plasma Folate, Vitamin B12, Homocyst(e)ine, and Colorectal Cancer Risk

Jing Ma, Meir J. Stampfer, Benedicte Christensen, Edward Giovannucci, David J. Hunter, Jia Chen, Walter C. Willett, Jacob Selhub, Charles H. Hennekens, Roy Gravel and Rima Rozen
Jing Ma
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Meir J. Stampfer
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Benedicte Christensen
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Edward Giovannucci
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David J. Hunter
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Jia Chen
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Walter C. Willett
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Jacob Selhub
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Charles H. Hennekens
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Roy Gravel
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Rima Rozen
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DOI:  Published September 1999
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    Fig. 1.

    Role of methionine synthase (MS) and MTHFR in folate/homocyst(e)ine/methionine metabolism.

Tables

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  • Table 1

    Frequency of MTR genotypes and age-adjusted risk of colorectal cancer by MTR genotype among participants of the Physicians’ Health Study (PHS) and the Health Professional Follow-up Study (HPFS)

    MTR genotypeCasesControlsOR95% CI
    N(%)N(%)
    PHS
     asp/asp 145(68)235(68)1.00ref.a
     asp/gly 61(29)95(27)1.040.71–1.53
     gly/gly 6(3)16(5)0.630.24–1.64
     Total212346
    HPFS
     asp/asp 103(72)82(63)1.00ref.
     asp/gly 37(26)42(32)0.710.42–1.20
     gly/gly 4(3)6(5)0.530.14–1.93
     Total144130
    PHS and HPFS
     asp/asp 248(70)317(66)1.00ref.
     asp/gly 98(28)137(29)0.920.67–1.25
     gly/gly 10(3)22(5)0.590.27–1.27
     Total356476
    • a ref., reference.

  • Table 2

    Age-adjusted mean of folate (geometric mean), B12, and homocyst(e)ine by case/control status and genotypes of MTR and MTHFR among the PHS participants

    CaseControls
    NMeanNMean
    MTR genotype
     Folate
      asp/asp1264.132184.29
      gly/asp534.17873.80
      gly/gly64.60143.88
     B12
      asp/asp126452218477
      gly/asp5349487476
      gly/gly654214506
     Homocyst(e)ine
      asp/asp11512.920012.3
      gly/asp4911.67911.9
      gly/gly612.81111.4
    MTHFR genotype
     Folate
      ala/ala814.541384.39
      val/ala813.871164.07
      val/val143.12a463.50a
     B12
      ala/ala81471138503
      val/ala81462116468
      val/val1443146440
     Homocyst(e)ine
      ala/ala7912.013512.2
      val/ala7812.311111.8
      val/val1317.6b4313.1
    • a P ≤ 0.05.

    • b P ≤ 0.01 for val/valgenotype versus ala/ala genotype.

  • Table 3

    Age-adjusted risk of colorectal cancer according to MTR and MTHFR genotypes and levels of folate and homocyst(e)ine among the PHS participants

    Folate (ng/ml)Homocyst(e)ine (mg/dl)
    Tertile 1Tertile 2 and 3Tertile 1 and 2Tertile 3
    MTR asp/asp or gly/asp
     Number51/102128/203100/18664/93
     OR (95% CI)0.84 (0.56–1.27)1.00 (ref)1.00 (ref)1.21 (0.81–1.82)
    MTR gly/gly
     Number3/43/104/72/4
     OR (95% CI)1.25 (0.27–5.69)0.51 (0.14–1.90)1.10 (0.31–3.90)1.05 (0.19–5.85)
      Pinteraction = 0.22  Pinteraction = 0.37
    MTHFR ala/ala or val/ala
     Number45/83117/171100/16757/79
     OR (95% CI)0.88 (0.56–1.36)1.00 (ref)1.00 (ref)1.16 (0.76–1.78)
    MTHFR val/val
     Number8/186/284/259/18
     OR (95% CI)0.57 (0.24–1.38)0.29 (0.12–0.73)0.25 (0.08–0.74)0.69 (0.29–1.62)
     Pinteraction = 0.16 Pinteraction = 0.24
  • Table 4

    Age-adjusted risk of colorectal cancer according to MTR genotype and alcohol intake among United States physicians and health professionals in the PHS and HPFS

    MTR genotypeAlcohol intake
    <1 drink/day≥1 drink/day
    asp/asp
     Number162/21086/104
     OR (95% CI)1.00 (ref.)1.04 (0.73–1.49)
    gly/asp
     Number57/8641/50
     OR (95% CI)0.88 (0.59–1.30)1.03 (0.64–1.63)
    gly/gly
     Number4/196/3
     OR (95% CI)0.27 (0.09–0.81)2.64 (0.65–10.82)
    Ptrend = 0.04Ptrend = 0.52
    Pinteraction = 0.04
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September 1999
Volume 8, Issue 9
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A Polymorphism of the Methionine Synthase Gene: Association with Plasma Folate, Vitamin B12, Homocyst(e)ine, and Colorectal Cancer Risk
Jing Ma, Meir J. Stampfer, Benedicte Christensen, Edward Giovannucci, David J. Hunter, Jia Chen, Walter C. Willett, Jacob Selhub, Charles H. Hennekens, Roy Gravel and Rima Rozen
Cancer Epidemiol Biomarkers Prev September 1 1999 (8) (9) 825-829;

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A Polymorphism of the Methionine Synthase Gene: Association with Plasma Folate, Vitamin B12, Homocyst(e)ine, and Colorectal Cancer Risk
Jing Ma, Meir J. Stampfer, Benedicte Christensen, Edward Giovannucci, David J. Hunter, Jia Chen, Walter C. Willett, Jacob Selhub, Charles H. Hennekens, Roy Gravel and Rima Rozen
Cancer Epidemiol Biomarkers Prev September 1 1999 (8) (9) 825-829;
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