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Folic acid supplementation for the prevention of recurrence of colorectal adenomas: metaanalysis of interventional trials

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Abstract

Conflicting data have emerged from preclinical and clinical studies that examined the relationship between folic acid and the risk of recurrence of colorectal adenomas. To determine precisely that relation, we planned this metaanalysis. We searched literature to identify interventional randomized, placebo-controlled studies where folic acid in specific dose and for specific duration was administered to evaluate its effect on the recurrence of adenomatous colorectal polyps. Five eligible trials were identified. The total number of patients with history of colorectal adenomas in the folate and the placebo groups was 805 and 775 patients, respectively. Our analysis showed that folate supplementation had no protective effects on the recurrence of colorectal adenomas [odds ratio = 1.08 (95% CI; 0.87, 1.33; P = 0.49)], nor has a positive outcome on the number of recurrent polyps per patient (P = 0.41). Examination of folic acid dose effect showed that the two studies that have used folic acid as 1 mg/day favored folic acid over placebo with an odds ratio of 0.62 (95% CI; 0.48, 0.80). However, the overall effect for all included studies was not significant [odds ratio = 0.78 (95% CI; 0.49, 1.24; P = 0.30)]. We found significant heterogeneity between trials, moreover, included trials exhibit inconsistency in methodological quality. The present metaanalysis has failed to show potential benefit for folate supplementation. Future trials should examine the effect of different dosage and duration. Moreover, the confounding effect of dietary and life style habits should be carefully controlled.

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References

  1. Benito E, Stiggelbout A, Bosch FX, et al. Nutritional factors in colorectal cancer risk: a case-control study in Majorca. Int J Cancer. 1991;49:161–7.

    Article  CAS  PubMed  Google Scholar 

  2. Meyer F, White E. Alcohol and nutrients in relation to colon cancer in middle-aged adults. Am J Epidemiol. 1993;138:225–36.

    CAS  PubMed  Google Scholar 

  3. Baron JA, Sandler RS, Haile RW, et al. Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst. 1998;90:57–62.

    Article  CAS  PubMed  Google Scholar 

  4. Paspatis GA, Kalafatis E, Oros L, et al. Folate status and adenomatous colonic polyps. A colonoscopically controlled study. Dis Colon Rectum. 1995;38:64–7. discussion 67-68.

    Article  CAS  PubMed  Google Scholar 

  5. Lashner BA, Provencher KS, Seidner DL, Knesebeck A, Brzezinski A. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology. 1997;112:29–32.

    Article  CAS  PubMed  Google Scholar 

  6. Song J, Medline A, Mason JB, Gallinger S, Kim YI. Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse. Cancer Res. 2000;60:5434–40.

    CAS  PubMed  Google Scholar 

  7. Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007;297:2351–9.

    Article  CAS  PubMed  Google Scholar 

  8. Sanjoaquin MA, Allen N, Couto E, Roddam AW, Key TJ. Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer. 2005;113:825–8.

    Article  CAS  PubMed  Google Scholar 

  9. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52:377–84.

    Article  CAS  PubMed  Google Scholar 

  10. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  11. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    CAS  PubMed  Google Scholar 

  12. Paspatis GA, Karamanolis DG. Folate supplementation and adenomatous colonic polyps. Dis Colon Rectum. 1994;37:1340–1.

    Article  CAS  PubMed  Google Scholar 

  13. Kim YI, Baik HW, Fawaz K, et al. Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Am J Gastroenterol. 2001;96:184–95.

    Article  CAS  PubMed  Google Scholar 

  14. Logan RF, Grainge MJ, Shepherd VC, Armitage NC, Muir KR. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology. 2008;134:29–38.

    Article  CAS  PubMed  Google Scholar 

  15. Figueiredo JC, Levine AJ, Grau MV, et al. Colorectal adenomas in a randomized folate trial: the role of baseline dietary and circulating folate levels. Cancer Epidemiol Biomarkers Prev. 2008;17:2625–31.

    Article  CAS  PubMed  Google Scholar 

  16. Jaszewski R, Misra S, Tobi M, et al. Folic acid supplementation inhibits recurrence of colorectal adenomas: a randomized chemoprevention trial. World J Gastroenterol. 2008;14:4492–8.

    Article  CAS  PubMed  Google Scholar 

  17. Majumdar AP, Kodali U, Jaszewski R. Chemopreventive role of folic acid in colorectal cancer. Front Biosci. 2004;9:2725–32.

    Article  CAS  PubMed  Google Scholar 

  18. Kim YI. Folate, colorectal carcinogenesis, and DNA methylation: lessons from animal studies. Environ Mol Mutagen. 2004;44:10–25.

    Article  CAS  PubMed  Google Scholar 

  19. Kim YI. Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut. 2006;55:1387–9.

    Article  CAS  PubMed  Google Scholar 

  20. Song J, Sohn KJ, Medline A, et al. Chemopreventive effects of dietary folate on intestinal polyps in Apc +/−Msh2−/− mice. Cancer Res. 2000;60:3191–9.

    CAS  PubMed  Google Scholar 

  21. Natarajan L, Flatt SW, Sun X, et al. Validity and systematic error in measuring carotenoid consumption with dietary self-report instruments. Am J Epidemiol. 2006;163:770–8.

    Article  PubMed  Google Scholar 

  22. Women's Health Initiative Study Group. Dietary adherence in the Women’s Health Initiative Dietary Modification Trial. J Am Diet Assoc. 2004;104:654–8.

    Google Scholar 

  23. Kristal AR, Andrilla CH, Koepsell TD, Diehr PH, Cheadle A. Dietary assessment instruments are susceptible to intervention-associated response set bias. J Am Diet Assoc. 1998;98:40–3.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Ezzeldin M. Ibrahim.

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Ibrahim, E.M., Zekri, J.M. Folic acid supplementation for the prevention of recurrence of colorectal adenomas: metaanalysis of interventional trials. Med Oncol 27, 915–918 (2010). https://doi.org/10.1007/s12032-009-9306-9

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  • DOI: https://doi.org/10.1007/s12032-009-9306-9

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