A total of 29,133 male smokers, aged 50-69 years, were recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in 1984-1988. The nationwide Finnish Cancer Registry (FCR) recorded 5944 incident cases of cancer in this cohort through the end of 1999. Compared with the FCR data of the entire Finnish male population of same age the standardized incidence ratio (SIR) of total cancer in the ATBC cohort was 1.55 [95% confidence interval (CI) 1.51-1.59]. There was a significant excess of established smoking-related malignancies, such as lung cancer (SIR 2.45, 95% CI 2.35-2.56), and cancers of the tongue, mouth, pharynx, larynx, oesophagus, pancreas, stomach, liver, urinary bladder and kidney. In addition to these sites, cancers of the prostate and colon were slightly more common in the ATBC cohort than in the total Finnish male population (SIR 1.10, 95% CI 1.04-1.18 and SIR 1.14, 95% CI 1.00-1.30, respectively). In conclusion, the risk of many cancers was significantly higher in the ATBC Study cohort compared with the total Finnish male population of same age. In addition to the well known smoking-related cancers, cigarette smoking may increase slightly the risk of colon and prostate cancer, too.

Malila N, Virtanen MJ, Virtamo J, Albanes D, Pukkala E.

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland. nea.malila@cancer.fi

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An alpha-tocopherol, beta-carotene supplementation trial (ATBC) and a chemoprevention trial with beta-carotene and retinoids (CARET trial) were conducted in the 1990s in populations at risk for the development of lung cancer. Both trials had to be discontinued due to significant increases in lung cancer and cardiovascular mortality. Clinical trials to test the cancer preventive effects of beta-carotene are still ongoing, and high concentrations of this provitamin are contained in numerous dietary supplements. Using a cell line derived from a human pulmonary adenocarcinoma (PAC) of Clara cell lineage and immortalized human small airway epithelial cells, our data show that low concentrations of beta-carotene that can be realistically expected in human tissues after oral administration caused a significant increase in intracellular cAMP and activated PKA, as well as in phosphorylation of ERK1/2 and CREB. Furthermore, the proliferation of cells was significantly stimulated by identical concentrations of beta-carotene as monitored by MTT assays. Control experiments with retinol also showed stimulation of cell proliferation and activation of PKA in both cell lines. In light of the fact that PAC is the leading type of lung cancer, these findings suggest that the growth promoting effects of beta-carotene on this cancer type observed in our experiments may have contributed to the unfortunate outcome of the ATBC and CARET trials. This interpretation is supported by the fact that elevated levels of cAMP in the cardiovascular system play a major role in the genesis of cardiovascular disease, which was also greatly promoted in the CARET trial. Our data challenge the widely accepted view that beta-carotene may be useful as a cancer preventive agent.

Al-Wadei HA, Takahashi T, Schuller HM.

Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.

The study was led by the Cochrane Hepato-Biliary Group at Copenhagen University Hospital in Denmark. The researchers first analyzed 68 studies involving 232,606 people and found no significant effect on mortality — neither good nor bad — linked to taking antioxidants. When they eliminated the lower-quality studies and looked only at the most trustworthy ones, they actually found a higher risk of death for people taking vitamins: 4 percent for those taking vitamin E, 7 percent for beta-carotene and 16 percent for vitamin A. The actual cause of death in most studies was unknown, however. Those findings are based on an analysis of 47 studies involving 180,938 people who were randomly assigned to get real vitamins or dummy pills. Some involved superdoses far exceeding the recommended daily amount of the compounds; others involved normal doses. The study’s senior author, Dr. Christian Gluud of Copenhagen University Hospital, said, “The main message is that prevention by beta carotene, vitamin A and vitamin E cannot be recommended. These three antioxidant supplements may increase mortality.”

Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis.
JAMA. 2007 Feb 28;297(8):842-57. Review.
PMID: 17327526 [PubMed - indexed for MEDLINE]