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

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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

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Abbreviations

CI:

Confidence interval

CRC:

Colorectal cancer

DFE:

Dietary folate equivalents

FFQ:

Food frequency questionnaire

MTHFR:

Methylenetetrahydrofolate reductase

OR:

Odds ratio

PPT:

Polyp prevention trial

RR:

Relative risk

SNP:

Single nucleotide polymorphism

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Acknowledgments

This study was funded by the Intramural Research Program, National Cancer Institute, NIH, Bethesda, MD. Dr Murphy is supported by the Ireland-Northern Ireland-National Cancer Institute Cancer Consortium and the Health Research Board of Ireland.

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Authors and Affiliations

  1. Cancer Prevention Fellowship Program, Office of Preventive Oncology, Bethesda, MD, USA

    Gwen Murphy, Leah B. Sansbury & Adeyinka Laiyemo

  2. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Gwen Murphy, Leah B. Sansbury, Adeyinka Laiyemo & Elaine Lanza

  3. Infection & Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., EPS 7067, Rockville, MD, 20892, USA

    Gwen Murphy

  4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Amanda J. Cross, Rachael Stolzenberg-Solomon & Arthur Schatzkin

  5. Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA

    Paul S. Albert

  6. Information Management Services, Inc., Rockville, MD, USA

    Zhuoqiao Wang

  7. Bioserve Biotechnologies, Ltd., Laurel, MD, USA

    Teresa Lehman, Aravind Kalidindi & Rama Modali

Authors
  1. Gwen Murphy
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  2. Leah B. Sansbury
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  12. Elaine Lanza
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Corresponding author

Correspondence to Gwen Murphy.

Additional information

Leah B. Sansbury, Amanda J. Cross, and Rachael Stolzenberg-Solomon have contributed equally to this work.

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Murphy, G., Sansbury, L.B., Cross, A.J. et al. Folate and MTHFR: risk of adenoma recurrence in the Polyp Prevention Trial. Cancer Causes Control 19, 751–758 (2008). https://doi.org/10.1007/s10552-008-9137-6

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  • DOI: https://doi.org/10.1007/s10552-008-9137-6

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