Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis

Our plain-English summary of Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis, by D. Papaioannou, K.L. Cooper, C. Carroll, et al (Colorectal Disease, 2011).

The study

• Authors: D. Papaioannou, K.L. Cooper, C. Carroll, D. Hind, H. Squires, P. Tappenden, R.F. Logan
• Journal: Colorectal Disease
• Published: 2011;13(10):1085-99
• Type of article: Meta-analysis, Systematic review
• Cited by: 50 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aim: Antioxidants, such as vitamin A, C and E, selenium and β-carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population.

Method: A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta-analysis was performed.

Results: Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n=148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13]. One study assessed the effect of antioxidants on adenoma formation (n=15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97-2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09-1.79, P=0.02) or vitamin E plus β-carotene (RR 1.63, 95% CI 1.01-2.63, P=0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos.

Conclusion: The review demonstrates that antioxidants (vitamin A, C and E, selenium and β-carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer.

© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

In plain English

This was a systematic review and meta-analysis of randomized controlled trials. It asked whether antioxidant supplements (vitamins A, C and E, selenium and beta-carotene) prevent colorectal cancer or colorectal adenomas in the general population. The authors found 12 trials. They included healthy people and groups with cardiovascular disease, smoking or asbestos exposure, skin cancer or atrophic gastritis. Pooling nine trials (148 922 participants), they found no difference in colorectal cancer (relative risk 1.00, 95% CI 0.88 to 1.13). Two trials of smokers or asbestos-exposed people were pooled as one group, with a relative risk of 1.07 (0.89 to 1.29). Asbestos-exposed workers were not analysed on their own. The only adenoma trial, in male smokers, showed no statistically significant overall effect (RR 1.47, 0.97 to 2.23). It did show higher adenoma risk with vitamin E alone and with vitamin E plus beta-carotene, which the authors said should be treated with caution. The authors concluded that antioxidants are not effective for preventing colorectal neoplasia in the general population. They noted short follow-up, heterogeneity between trials and unsystematic adenoma detection.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review and meta-analysis of randomized controlled trials
• Who was studied: 12 randomized trials (data from 13 articles), published 1996 to 2009. Each randomized between 216 and 39 876 participants, in the USA, the UK, France, Finland, China and multi-national settings. Groups studied were healthy people and people with cardiovascular disease, smoking or asbestos exposure, skin cancer, or atrophic gastritis.
• Exposure: Antioxidant supplements (vitamin A, C and E, selenium or beta-carotene), alone, combined with each other, or combined with other agents, compared with placebo or no antioxidant. Asbestos exposure was a characteristic of participants in one included trial (CARET: smokers, former smokers and workers exposed to asbestos). It was not the intervention studied.
• Main results:
  • Across nine trials comparing any antioxidant with no antioxidant (148 922 participants), there was no difference in colorectal cancer occurrence: RR 1.00, 95% CI 0.88 to 1.13.
  • In the combined subgroup of smokers or people with asbestos exposure (two trials), colorectal cancer occurred in 392 of 31 266 people on antioxidants and 198 of 16 181 controls. The RR was 1.07 (95% CI 0.89 to 1.29). The healthy-population subgroup had RR 1.01 (0.86 to 1.19) and the cardiovascular disease subgroup RR 0.99 (0.68 to 1.42). The authors said these subgroup results are uncertain because of heterogeneity.
  • In the one trial assessing adenomas (ATBC, male smokers, 15 538 participants), any antioxidant vs placebo showed no statistically significant difference in developing at least one adenoma: RR 1.47, 95% CI 0.97 to 2.23, P = 0.07.
  • In that trial, adenomas occurred in 47 of 3890 men given vitamin E alone vs 27 of 3887 on placebo. Table 2 gives RR 1.74 (95% CI 1.09 to 2.79).
  • Men given vitamin E plus beta-carotene in the same trial had RR 1.63 (95% CI 1.01 to 2.63, P = 0.04) for adenoma vs placebo. The authors said these adenoma findings should be treated with caution.
• The authors' conclusion: The authors concluded that antioxidants, as single agents or in combination, are not effective in the chemoprevention of colorectal neoplasia in the general population. They added that this questions their use in future chemoprevention trials.
• Limitations the authors state:
  • In the only adenoma trial, adenomas were not found by systematic screening but from pathology laboratory files, so the adenoma counts are uncertain.
  • Follow-up of 5 to 12 years may be too short to detect an effect on colorectal cancer.
  • The significant adenoma results came from small numbers of participants and events, and from many separate analyses not corrected for repeated testing.
  • There was high heterogeneity between studies, and the funnel plot for the main analysis was asymmetrical, suggesting possible bias.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer.

Medical terms in this study, explained in our Lexicon: Colorectal Cancer, Systematic Review, Meta-Analysis, Neoplasm, Relative Risk, confidence interval.

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