Early detection and prevention of lung cancer

Lung cancer remains the leading cause of cancer death in the United States and is one of the world's leading causes of preventable death, Technologic advances have brought new modalities that may be useful for the early detec tion of lung cancer. However, because of the large number of persons at inc reased risk for lung cancer, screening is a formidable task. There are seve ral risk factors that can be identified, including potential susceptibility factors, which may aid in pinpointing individuals who need to participate in regular screening programs. Aside from recognized environmental exposure s including cigarette smoking, there are a number of genetic and metabolic susceptibility factors that have been examined. These include polymorphisms in the cytochrome p450 enzymes and the metabolizing capability of glutathi one s-transferase or acetylation, Additionally, defects in DNA repair and i n bleomycin sensitivity assays may also aid in identifying individuals who are at an increased risk for lung cancer, Additional work has been done in the area of characterizing the molecular alterations in the bronchial epith elium in high-risk smokers. This manuscript addresses only selected molecul ar alterations that have been examined in preneoplastic bronchial epitheliu m. In addition to mutations in the k-ras oncogene and the p53 gene, which a re frequently seen in malignancy, alterations in the p16 gene, microsatelli te instability and loss of heterozygocity are also promising potential mark ers of preneoplasia, The hnRNP A2/B1 gene also shows some promising increas ed expression in preneoplasia. Lung cancer prevention has made some strides . A number of trials with molecular and morphologic intermediate endpoints have been conducted and have suggested that some of the molecular alteratio ns and morphologic alterations are reversible. However, the rate of spontan eous regression of these lesions is, as yet, uncharacterized. Two recent la rge studies, the beta-carotene and retinol efficacy trial (CARET) trial con ducted in the United States and the Alpha-Tocopherol Beta Carotene (ATBC) t rial conducted in Finland, both demonstrated an unexpected increased risk f or lung cancer associated with beta-carotene supplementation. The EUROSCAN trial evaluation of vitamin A and N-acetylcystine also showed no benefit to supplementation in reducing risk for lung cancer. Results from the Intergr oup study of 13-cis-retinoic acid are pending, and plans are underway for a n Intergroup trial studying high selenium yeast to reduce lung cancer risk. Hopefully, the combination of identifying markers of increased risk among the numerous current and former smokers will identify high-risk populations to participate in future trials of promising agents that may lead to reduc tion in incidence and mortality of the leading cause of cancer death. (C) 2 000 Lippincott Williams & Wilkins, Inc.