Prevention of lung cancer.
Lung cancer is the major cause of death in industrialized western societies. Its link to tobacco abuse is well established and efforts should be made to eliminate this potent environmental carcinogen. The concept of chemoprevention, the use of agents to inhibit and reverse lung cancer carcinogenesis, has great appeal. The CARET study, conducted in 18,000 high-risk smokers in the US, found that a combination of beta-carotene and retinyl palmitate resulted in a 28% increase in the incidence of lung cancer. A similar study conducted in Finland, the ATBC trial utilizing alpha tocopherol and beta-carotene, had similar findings for the group taking beta-carotene. These two trials have caused a rethinking of the use of natural compounds as chemoprevention agents. These agents should no longer be regarded as harmless, but as having potential toxicities. A new approach in the chemoprevention of cancer has been the concept of surrogate endpoints, biological changes that are on the pathway to cancer. Trials are underway to determine what are appropriate surrogate endpoints for lung cancer chemoprevention trials.
Goodman
G E
GE
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ggoodman@fhcrc.org
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002338:Carotenoids / Q000627:therapeutic use; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002986:Clinical Trials as Topic; D003043:Cocarcinogenesis; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004224:Diterpenes; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D000077276:Lycopene; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000175:diagnosis / Q000473:pathology / Q000517:prevention & control; D012176:Retinoids / Q000009:adverse effects / Q000627:therapeutic use; D000084562:Retinyl Esters; D012307:Risk Factors; D012643:Selenium / Q000627:therapeutic use; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D000074606:Smoking Prevention; D014131:Trace Elements / Q000627:therapeutic use; D016896:Treatment Outcome; D014801:Vitamin A / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use; D019207:beta Carotene / Q000009:adverse effects / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D002338:Carotenoids; D019363:Cytochrome P-450 CYP1A1; D004224:Diterpenes; D005419:Flavonoids; D005982:Glutathione Transferase; D000077276:Lycopene; D012176:Retinoids; D000084562:Retinyl Esters; D012643:Selenium; D014131:Trace Elements; D014801:Vitamin A; D014810:Vitamin E; D019207:beta Carotene; C014794:retinol palmitate