Vitamin A Chemoprevention of Lung Cancer

Abstract

This article describes an ongoing short-term biomarker study of Vitamin A in subjects at high risk for lung cancer. Workers exposed to asbestos and cigarettes have a markedly increased risk of developing lung cancer and parenchymal fibrosis. Epidemiologic and experimental studies have shown that dietary vitamin A has significant anticancer and immunomodulatory effects (1-6). However, whether intervention with supplemental vitamin A can reduce the mortality or morbidity from either disease and the mechanisms involved remains unclear. Airway metaplasia on bronchial biopsy and inflammation on bronchoalveolar lavage (BAL) are considered potential markers for the development of lung cancer and parenchymal fibrosis respectively. Our prior clinical studies (see below) have shown an high incidence of both of these lesions in asbestos-exposed subjects, findings consistent with the idea that the processes of inflammation and carcinogenesis are linked. We have hypothesized that 1) the vitamin A intervention may reduce both bronchial metaplasia and lung inflammation, 2) the mechanism of this effect may be through modulation of relevant pulmonary cytokines, growth factors, and/or oncogenes, and 3) local lung vitamin A status may be a key modifiable host determinant or biomarker of susceptibility. We are performing a double-blind placebo controlled 6 month trial of combination 0-carotene and retinol in 50 subjects at high risk for both lung cancer and parenchymal fibrosis to address these hypotheses. This study should provide valuable data on whether vitamin A can modify potential early markers of lung cancer and fibrosis, the mechanisms involved, and the role of local vitamin A. The findings may lead to effective preventive strategies for lung cancer.