Cancer Causes & Control

, Volume 19, Issue 7, pp 751–758

Folate and MTHFR: risk of adenoma recurrence in the Polyp Prevention Trial

  • Gwen Murphy
  • Leah B. Sansbury
  • Amanda J. Cross
  • Rachael Stolzenberg-Solomon
  • Adeyinka Laiyemo
  • Paul S. Albert
  • Zhuoqiao Wang
  • Arthur Schatzkin
  • Teresa Lehman
  • Aravind Kalidindi
  • Rama Modali
  • Elaine Lanza
Original Paper



Low dietary folate intake has been associated with colorectal cancer risk and adenoma recurrence. A C/T transition at position 677 in the gene encoding methlylenetetrahydrofolate reductase (MTHFR C677T) has been reported to interact with folate intake to modulate colorectal adenoma recurrence or cancer risk.


We investigated the association between MTHFR, total folate, and the risk of colorectal adenoma recurrence in the Polyp Prevention Trial. We compared 625 individuals with any adenoma recurrence after 4 years (266 individuals with multiple (≥2) recurrent adenomas and 101 individuals with advanced adenoma recurrence) to 978 individuals with no adenoma recurrence. Odds ratios (OR) and 95% confidence intervals (CI) for risk of adenoma recurrence were calculated using unconditional logistic regression. We also investigated effect modification of the MTHFR genotype associations by total folate intake.


In general, no statistically significant associations were found between quartile of folate intake (dietary or total) and adenoma recurrence. The MTHFR CT genotype was associated with a significantly increased risk of multiple adenoma recurrence (OR: 1.34, 95% CI: 1.00, 1.81). No significant interaction was noted for total folate and MTHFR genotype, though an increased risk of recurrence noted for the MTHFR CT genotype was statistically significant only for those individuals with below median intake of total folate.


We report that the MTHFR 677 CT genotype was associated with increased risk of adenoma recurrence (specifically multiple adenoma recurrence) 4 years after polypectomy.


Folate Methlylenetetrahydrofolate reductase Adenoma 



Confidence interval


Colorectal cancer


Dietary folate equivalents


Food frequency questionnaire


Methylenetetrahydrofolate reductase


Odds ratio


Polyp prevention trial


Relative risk


Single nucleotide polymorphism


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Gwen Murphy
    • 1
    • 2
    • 3
  • Leah B. Sansbury
    • 1
    • 2
  • Amanda J. Cross
    • 4
  • Rachael Stolzenberg-Solomon
    • 4
  • Adeyinka Laiyemo
    • 1
    • 2
  • Paul S. Albert
    • 5
  • Zhuoqiao Wang
    • 6
  • Arthur Schatzkin
    • 4
  • Teresa Lehman
    • 7
  • Aravind Kalidindi
    • 7
  • Rama Modali
    • 7
  • Elaine Lanza
    • 2
  1. 1.Cancer Prevention Fellowship ProgramOffice of Preventive OncologyBethesdaUSA
  2. 2.Center for Cancer ResearchNational Cancer InstituteBethesdaUSA
  3. 3.Infection & Immunoepidemiology Branch, Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleUSA
  4. 4.Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaUSA
  5. 5.Biometric Research Branch, Division of Cancer Treatment and DiagnosisNational Cancer InstituteBethesdaUSA
  6. 6.Information Management Services, Inc.RockvilleUSA
  7. 7.Bioserve Biotechnologies, Ltd.LaurelUSA

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