CHEMOPREVENTION OF LUNG CANCER: The Rise and Demise of Beta-Carotene

Abstract

Beta-carotene and retinoids were the most promising agents against common cancers when the National Cancer Institute mounted a substantial program of population-based trials in the early 1980s. Both major lung cancer chemoprevention trials not only showed no benefit, but had significant increases in lung cancer incidence and in cardiovascular and total mortality. A new generation of laboratory research has been stimulated.Rational public health recommendations at this time include: 1. Five-A-Day servings of fruits and vegetables, a doubling of current mean intake; 2. systematic investigation of the covariates of extremes of fruit and vegetable intake; 3. discouragement of beta-carotene supplement use, due to adverse effects in smokers and no evidence of benefit in non-smokers; 4. multilevel research to develop and evaluate candidate chemoprevention agents to prevent lung and other common cancers; and 5. continued priority for smoking prevention, smoking cessation, and avoidance of known carcinogens in the environment.

The effect of β-carotene on common cold incidence is modified by age and smoking: evidence against a uniform effect in a nutrient–disease relationship

“…However, the ATBC and CARET studies found, paradoxically, that β-carotene supplementation increased the incidence of lung cancer, thereby refuting the conclusions based on the observational studies. 15,19 Similarly, meta-analyses of vitamin E trials 20,21 refuted the cohort studies suggesting that increased vitamin E intake would reduce the risk of cardiovascular diseases in large population groups.…”

Statement on the safety of β‐carotene use in heavy smokers

“…In the past, high serum β-carotene levels have been associated with a decrease in incidence of cancer, including lung cancer, in humans (Mayne, 1996;Ziegler et al, 1996). However, the ATBC study and CARET trials (ATBC Study group, 1994;Omenn et al, 1996a;1996b;Omenn, 1998) unexpectedly revealed that heavy smokers (at least 1 package/day for 36 years on average) receiving long-term β-carotene (20 mg/day) supplementation (ATBC) or β-carotene (30 mg/day) + retinol (25 000 International Unit (IU) vitamin A) supplementation (CARET), showed increased rather than decreased incidences of lung cancer.…”

The crucial role of the public health sciences in the postgenomic era

“…Examples are antioxidant vitamins (beta-carotene, C, E), vitamin A and other retinoids, folic acid, and inducers of glutathione. 11,12 For infectious agents, vaccines can be highly effective preventive interventions. And for environmental and occupational risk reduction, it is feasible to monitor emissions, exposures, and subclinical and clinical effect rates after actions are taken.…”