Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Patients who undergo polypectomy are at increased risk of adenoma recurrence. The preventive potential of vitamins (A, C and E) and selenium supplementation represent an interesting opportunity for colorectal cancer prevention.
To assess the efficacy of a combination of these micronutrients in reducing the incidence of recurrent adenomas in subjects on post-polypectomy endoscopic follow-up, a double-blind placebo-controlled randomized trial was started in Italy in 1988. A total of 411 patients were randomized to receive either an active compound (200 μg selenium, 30 mg zinc, 2 mg vitamin A, 180 mg vitamin C, 30 mg vitamin E) or a placebo daily for 5 years. Of them, 330 had follow-up colonoscopy (164 in the intervention and 166 in the placebo group).
After a median follow-up of 4 years (range 1–15 years), 100 patients had recurrence: 38 in the intervention and 62 in the placebo arm. The 15-year cumulative incidence of recurrence was 48.3 % in the intervention and 64.5 % in the placebo arm (HR = 0.59; log-rank P = 0.009). A 39 % reduction of the risk of recurrence was observed in the intervention compared to the placebo group (adjusted HR = 0.61; 95 % CI 0.41–0.92): the risk reduction was similar for small tubular (adjusted HR = 0.61; 95 % CI 0.37–0.99) and advanced adenomas (adjusted HR = 0.50; 95 % CI 0.24–1.01).
Our study showed a statistically significant effect of antioxidant supplementation on adenoma recurrence. Further clinical trials are needed to address the role of antioxidants in subgroups of subjects at increased risk for colorectal cancer.
- Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:65–81. CrossRef
- Leslie A, Carey FA, Pratt NR, Steele RJ. The colorectal adenoma-carcinoma sequence. Br J Surg. 2002;89:845–60. CrossRef
- Cairns SR, Scholefield JH, Steele RJ, et al.; British Society of Gastroenterology; Association of Coloproctology for Great Britain and Ireland. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010;59:666–89.
- Salonen JT, Alfthan G, Huttunen JK, Puska P. Association between serum selenium and the risk of cancer. Am J Epidemiol. 1984;120:342–9.
- Salonen JT, Salonen R, Lappeteläinen R, Mäenpää PH, Alfthan G, Puska P. Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data. Br Med J. 1985;290:417–20. CrossRef
- Nomura A, Heilbrun LK, Morris JS, Stemmermann GN. Serum selenium and the risk of cancer, by specific sites: case-control analysis of prospective data. J Natl Cancer Inst. 1987;79:103–8.
- Wald NJ, Thompson SG, Densem JW, Boreham J, Baley A. Serum beta-carotene, and subsequent the risk of cancer: results from the BUPA study. Br J Cancer. 1988;57:428–33. CrossRef
- Birt DF, Lawson TA, Julius AD, Runice CE, Salmasi S. Inhibition by dietary selenium of colon cancer induced in the rat by bis (2-oxopropil) nitrosamine. Cancer Res. 1982;42:4455–9.
- Reddy BS, Sugie S, Maruyama S, El-Bayomy K, Marra P. Chemoprevention of colon carcinogenesis by dietary organoselenium, benzylselenocyanate, in F344 rats. Cancer Res. 1987;47:5901–4.
- Dion PW, Bright-See EB, Smith CC, Bruce WR. The effect of dietary ascorbic acid and a-Tocopherol on fecal mutagenicity. Mutat Res. 1982;102:27–37. CrossRef
- Song MK, Adham NF, Heng MC, Costea NV, Heng MK, Ament ME. Metabolic alterations of zinc and prostaglandins in both human and animal colonic tumor cells. J Am Coll Nutr. 1995;14:473–9.
- Bonelli L, Camoriano A, Ravelli P, Missale G, Bruzzi P, Aste H. Reduction of the incidence of recurrent adenomas of the large bowel by means of antioxidants. In: Palmieri Y, editor. Proceedings of International Selenium Tellurium Development Association. Brussels, Belgium: Se-Te Press; 1998. p. 91–4.
- Freedman LS, Green SB. Statistical design for investigating several interventions in the same study: methods for cancer prevention trials. J Natl Cancer Inst. 1990;82:910–4. CrossRef
- Morson BC, Sobin LH. Histological typing of intestinal tumours. Geneva: World Health Organization; 1976. (International histological classification of tumours no. 15).
- Jass J, Sobin LH. Histological typing of intestinal tumours. II ed. Berlin: Springer; 1989. CrossRef
- Morson BC, Bussey HT. Magnitude of risk for cancer in patients with colorectal adenomas. Br J Surg. 1985;72:S23–5. CrossRef
- McKeown-Eyssen G, Holloway C, Jazmaji V, Bright-See E, Dion P, Bruce WR. A randomized trial of vitamins C and E in the prevention of recurrence of colorectal polyps. Cancer Res. 1988;48:4701–5.
- Greenberg ER, Baron JA, Tosteson TD, Polyp Prevention Study Group, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. N Engl J Med. 1994;331:141–7. CrossRef
- Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81. CrossRef
- Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patients: II Analysis and examples. Br J Cancer. 1977;35:1–39. CrossRef
- Cox DR. Regression model and life-tables. J R Stat Soc B. 1972;34:187–220.
- Malila N, Virtamo J, Virtanen M, Albanes D, Tangrea JA, Huttunen JK. The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers. Cancer Epidemiol Biomarkers Prev. 1999;8:489–93.
- Albanes D, Malila N, Taylor PR, Huttunen JK, Virtamo J, Edwards BK. Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland). Cancer Causes Control. 2000;11:197–205. CrossRef
- Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev. 2008;3:CD004183. Review.
- Baron JA, Cole BF, Mott L, Haile R, Grau M, Church TR, et al. Neoplastic and antineoplastic effects of beta-carotene on colorectal adenoma recurrence: results of a randomized trial. J Natl Cancer Inst. 2003;95:717–22. CrossRef
- Roncucci L, Di Donato P, Carati L, Colorectal Cancer Study Group of the University of Modena and the Health Care District 16, et al. Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Dis Colon Rectum. 1993;36:227–34. CrossRef
- Hofstad B, Almendingen K, Vatn M, et al. Growth and recurrence of colorectal polyps: a double-blind 3-year intervention with calcium and antioxidants. Digestion. 1998;59:148–56. CrossRef
- Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 1996;276:1957–63. CrossRef
- Duffield-Lillico AJ, Reid ME, Turnbull BW, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol Biomarkers Prev. 2002;11:630–9.
- Reid ME, Duffield-Lillico AJ, Sunga A, Fakih M, Alberts DS, Marshall JR. Selenium supplementation and colorectal adenomas: an analysis of the nutritional prevention of cancer trial. Int J Cancer. 2006;118:1777–81. CrossRef
- Jacobs ET, Jiang R, Alberts DS, Greenberg ER, Gunter EW, Karagas MR. Selenium and colorectal adenoma: results of a pooled analysis. J Natl Cancer Inst. 2004;96:1669–75. CrossRef
- Peters U, Chatterjee N, Church TR, et al. High serum selenium and reduced risk of advanced colorectal adenoma in a colorectal cancer early detection program. Cancer Epidemiol Biomarkers Prev. 2006;15:315–20. CrossRef
- Stewart MS, Davis RL, Walsh LP, Pence BC. Induction of differentiation and apoptosis by sodium selenite in human colonic carcinoma cells (HT29). Cancer Lett. 1997;117:35–40. CrossRef
- Goulet AC, Chigbrow M, Frisk P, Nelson MA. Selenomethionine induces sustained ERK phosphorylation leading to cell–cycle arrest in human colon cancer cells. Carcinogenesis. 2005;26:109–17. CrossRef
- Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial
Journal of Gastroenterology
Volume 48, Issue 6 , pp 698-705
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Large bowel
- Recurrent adenoma
- Industry Sectors
- Author Affiliations
- 1. Secondary Prevention and Screening, IRCCS AOU San Martino-IST, Largo R. Benzi, 10, 16132, Genoa, Italy
- 4. Office of the Scientific Director, Ospedali Galliera, Genoa, Italy
- 10. AOU San Martino-IST (Unit of Pathology), Genoa, Italy
- 5. Gastroenterology Unit, Ospedali Galliera, Genoa, Italy
- 8. Unit of Surgical Endoscopy, University of Brescia, Brescia, Italy
- 2. Endoscopy Unit, IRCCS AOU San Martino-IST, Genoa, Italy
- 6. Pathology Unit, Ospedali Galliera, Genoa, Italy
- 9. Pathology Unit, Spedali Civili, Brescia, Italy
- 7. Medical Oncology Unit, Ospedali Galliera, Genoa, Italy
- 3. Clinical Epidemiology Unit, IRCCS AOU San Martino-IST, Genoa, Italy