Meta-analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancer
C. CARROLL
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorK. COOPER
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorD. PAPAIOANNOU
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorD. HIND
Health Services Research, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
Search for more papers by this authorP. TAPPENDEN
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorH. PILGRIM
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorA. BOOTH
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorC. CARROLL
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorK. COOPER
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorD. PAPAIOANNOU
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorD. HIND
Health Services Research, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK
Search for more papers by this authorP. TAPPENDEN
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorH. PILGRIM
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorA. BOOTH
Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
Search for more papers by this authorAbstract
Aliment Pharmacol Ther 31, 708–718
Summary
Background Folic acid has been identified as a possible agent for the chemoprevention of colorectal cancer.
Aim To assess the effectiveness of folic acid in reducing the recurrence of adenomas (precursors of colorectal cancer) among populations with a history of adenomas and the incidence of colorectal cancer within average-risk populations.
Methods Systematic review of randomized controlled trials comparing folic acid alone, or with other agents, vs. placebo. Eight databases were searched for relevant trials. Meta-analysis was performed.
Results The literature search retrieved 3785 citations. Six studies met the inclusion criteria. Meta-analysis of three studies in individuals with a history of adenomas showed no statistically significant difference in the relative risk of adenoma recurrence (RR 0.93, P = 0.27). A sensitivity analysis of the two higher quality trials changed the direction of effect (RR 1.16, P = 0.11). Meta-analysis of three trials in general populations demonstrated no statistically significant effect on the relative risk of colorectal cancer (RR 1.13, P = 0.54). In all three analyses, outcome event rates were higher in individuals receiving folic acid.
Conclusion There is no evidence that folic acid is effective in the chemoprevention of colorectal adenomas or colorectal cancer for any population.
References
- 1 Bond J. Colorectal Cancer Update. Prevention, treatment, screening and surveillance for high-risk groups. Med Clin North Am 2000; 84: 1163–82.
- 2 Ferlay J, Bray F, Pisani P, et al. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase no.5, version 2.0. Lyon: IARCPress, 2004.
- 3 Office for National Statistics. MB1 No. 37: Registrations of cancer diagnosed in 2006, England. Available at: http://www.statistics.gov.uk/StatBase/Product.asp?vlnk=8843. London: 2008.
- 4 Welsh Cancer Intelligence and Surveillance Unit. Cancer incidence in Wales 2003–2007. Available at: http://www.wcisu.wales.nhs.uk. 2009.
- 5 Gionvannucci E, Stampfer M, Colditz G, et al. Folate, methionine, and alcohol intake and the risk of colorectal adenoma. J Nat Cancer Inst 1993; 85: 875–84.
- 6 National Institute for Health and Clinical Excellence (NICE). Guidance on Cancer Services: Improving Outcomes in Colorectal Cancers (Manual Update). NICE, London, 2004.
- 7 Bishop D, Hall N. The genetics of colorectal cancer. Eur J Cancer 1994; 30A: 1946–56.
- 8 Aaltonen L, Salovaara R, Kristo P, et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 1998; 338: 1481–7.
- 9 Hill M, Morson B, Bussey H. Aetiology of adenoma-carcinoma sequence in large bowel. Lancet 1992; 8058: 245–7.
- 10 Ramsoekh D, Van Leerdam ME, Wagner A, Kuipers EJ. Detection and management of hereditary non-polyposis colorectal cancer (Lynch syndrome). Aliment Pharmacol Ther 2007; 26(Suppl. 2): 101–11.
- 11 Centre for Reviews and Dissemination (CRD) UoY. The management of colorectal cancers. Effective Health Care 2004; 8: 1–12.
- 12 Leslie A, Carey F, Pratt N, et al. The colorectal-adenoma carcinoma sequence. Br J Surgery 2002; 89: 845–60.
- 13 Stryker S, Wolff B, Culp C, Libbe S, Ilstrup D, MacCarty R. Natural history of untreated colonic polyps. Gastroenterology 1987; 93: 1009–13.
- 14 Flossmann E, Rothwell P. British Doctors Aspirin Trial and the UK-TIA Aspirin Trial. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 2007; 369: 1603–13.
- 15 Atkin W, Saunders B. Surveillance guidelines after removal of colorectal adenomatous polyps. Gut 2002; 51(Suppl. 5): V6–9.
- 16 Cancer Research UK, 2008.
- 17 Cooper K, Pilgrim H, Carroll C, et al. Chemoprevention of colorectal cancer: systematic review and economic model. Health Technol Assess 2010 (Epub ahead of print).
- 18 Dube C, Rostom A, Lewin G, et al. The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007; 146: 365–75.
- 19 Rostom A, Dube C, Lewin G, et al. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007; 146: 376–89.
- 20 Asano T, McLeod R. Non steroidal anti-inflammatory drugs (NSAID) and Aspirin for preventing colorectal adenomas and carcinomas. Cochrane Database Syst Rev 2004; 2: CD004079.
- 21 Weingarten M, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2008: CD003548.
- 22 Shaukat A, Scouras N, Schunemann HJ. Role of supplemental calcium in the recurrence of colorectal adenomas: a meta-analysis of randomized controlled trials. Am J Gastro 2005; 100: 390–4.
- 23 Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev 2008: CD004183.
- 24 Bjelakovic G, Nagorni A, Nikolova D, Simonetti RG, Bjelakovic M, Gluud C. Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma. Aliment Pharmacol Ther 2006; 24: 281–91.
- 25 Kim Y-I. Folate, colorectal carcinogenesis and DNA methylation: lessons from animal studies. Environ Mol Mutagen 2004; 44: 10–25.
- 26 Choi S, Mason J. Folate status: effects on pathways of colorectal carcinogenesis. J Nutr 2002; 132(S): 2413S–8S.
- 27 Giovannucci E. Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr 2002; 132(S): 2350S–5S.
- 28 Sanjoaquin M, Allen N, Couto E, et al. Folate intake and colorectal cancer risk: a metaanalytical approach. Int J Cancer 2005; 113: 825–8.
- 29 Paspatis G, Kalafatis E, Oros L, et al. Folate status and adenomatous colonic polyps. A colonoscopically controlled study. Dis Colon Rectum 1995; 38: 64–7.
- 30 Baron J, Sandler R, Haile R, et al. Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst 1998; 90: 57–62.
- 31 Fife J, Raniga S, Hider P, Frizelle F. Folic acid supplementation and colorectal cancer risk: a meta-analysis. Col Dis 2009 [Epub ahead of print].
- 32 Scottish Intercollegiate Guidelines Network. Search filters: randomised controlled trials. Available at: http://www.sign.ac.uk/methodology/filters.html#random
- 33 NHS CRD. NHS Centre for Reviews and Dissemination. Report 4: Undertaking Systematic Reviews of Research on Effectiveness; CRD’s Guidance for Those Carrying out or Commissioning Reviews. New York: University of York, 2009.
- 34 Review Manager (RevMan). [Computer Program]. Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration 2008.
- 35 Montori V, Guyatt G. Intention-to-treat principle. CMAJ 2001; 165: 1339–41.
- 36 Hollis S, Campbell F. What is meant by intention to treat analysis? Survey of published randomised controlled trials BMJ 1999; 319: 670–4.
- 37 Logan R, Grainge M, Shepherd E, et al. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 2008; 134: 29–38.
- 38 Cole B, Baron J, Sandler R, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007; 297: 2351–9.
- 39 Zhang S, Cook N, Albert C, et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA 2008; 300: 2012–21.
- 40 Zhu S, Mason J, Yaol S, et al. The effect of folic acid on the development of stomach and other gastrointestinal cancers. Chin Med J 2003; 116: 15–9.
- 41 Baron J, Cole B, Sandler R, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003; 348: 891–9.
- 42 Cole B, Baron J, Sandler R, et al. A randomized trial of folic acid to prevent colorectal adenomas. Proc Am Assoc Cancer Res Annu Meet 2005; 46: 4399.
- 43 Zhu S, Mason J, Shi Y, et al. The interventional effect of folic acid on the development of gastric and other gastrointestinal cancers - Clinical trial and follow-up for seven years. Chinese Journal of Gastroenterology 2002; 7: 73–8.
- 44 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.
- 45 Lonn E, Yusuf S, Arnold J, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. New Eng J Med 2006; 354: 1567–77.
- 46 Lonn E, Held C, Arnold J, et al. Rationale, design and baseline characteristics of a large, simple, randomised trial of combined folic acid and vitamin B6 and B12, in high-risk patients: the Heart Outcomes Prevention Evaluation (HOPE)-2 trial. Can J Cardiol 2006; 22: 47–53.
- 47 Tierney J, Stewart L. Investigating patient exclusion bias in meta-analysis. Int J Epidemiol 2005; 34: 79–87.
- 48 Figueiredo J, Grau M, Halle R, et al. Folic acid and risk of prostate cancer: results from a randomized controlled trial. J Natl Cancer Inst 2009; 1010: 432–5.
- 49 Ulrich C, Potter J. Folate supplementation: too much of a good thing? Cancer Epidemiol Biomarkers Prev 2006; 15: 189–93.
- 50 Bjelakovic G, Nikolova D, Simonetti R, et al. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004; 364: 1219–28.
- 51 Kim Y.-I. Will mandatory folic acid fortification prevent or promote cancer? Am J Clin Nutr 2004; 80: 1123–8.
- 52 McKay J, Williams E, Mathers J. Gender specific modulation of tumorigenesis by folic acid supply in Apc+/Min mouse during early neonatal life. Brit J Nutr 2008; 99: 550–8.
- 53 Mathers J. Folate intake and bowel cancer risk. Genes Nutr 2009; 4: 173–8.
- 54 Mason J, Dickstein A, Jacques P, et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev 2007; 16: 1325–9.
- 55 Smith A, Kim Y-I, Refsum H. Is folic acid good for everyone? Am J Clin Nutr 2008; 87: 517–33.
- 56 Kim Y-I. Folic acid supplementation and cancer risk. Point. Cancer Epidemiol Biomarkers Prev 2008; 17: 2220–5.
- 57 Ulrich C. Folate and cancer prevention – Where to next? Counterpoint Cancer Epidemiol Biomarkers Prev 2008; 17: 2226–30.
- 58 Eichholzer M, Tonz O, Zimmerman R. Folic acid: a public health challenge. Lancet 2006; 367: 1352–61.
- 59 McGauran A. UK food agency reaffirms its advice that addition of folic acid to flour should be compulsory. BMJ 2009; 339: b4369.
- 60 Tedstone A, Browne M, Harrop L, et al. Fortification of selected foodstuffs with folic acid in the UK: consumer research carried out to inform policy recommendations. J Public Health 2008; 30: 23–9.