title: Predictors of lung cancer among asbestos-exposed men in the {beta}-carotene and retinol efficacy trial.
abstract: Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The beta-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9-17 years. Lung cancer incidence for 1989-2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years' exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.
authors.affiliation: Occupational and Environmental Medicine Program and the Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA. mark.cullen@yale.edu
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cullen
authors.forename: Matt J
authors.initials: MJ
authors.lastname: Barnett
authors.forename: John R
authors.initials: JR
authors.lastname: Balmes
authors.forename: Brenda
authors.initials: B
authors.lastname: Cartmel
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Redlich
authors.forename: Carl A
authors.initials: CA
authors.lastname: Brodkin
authors.forename: Scott
authors.initials: S
authors.lastname: Barnhart
authors.forename: Linda
authors.initials: L
authors.lastname: Rosenstock
authors.forename: Gary E
authors.initials: GE
authors.lastname: Goodman
authors.forename: Sam P
authors.initials: SP
authors.lastname: Hammar
authors.forename: Mark D
authors.initials: MD
authors.lastname: Thornquist
authors.forename: Gilbert S
authors.initials: GS
authors.lastname: Omenn
mesh_terms: D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D001195:Asbestosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D016273:Occupational Exposure / Q000009:adverse effects*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D013902:Radiography, Thoracic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D014481:United States / Q000453:epidemiology; D014801:Vitamin A / Q000008:administration & dosage; D019207:beta Carotene / Q000008:administration & dosage
chemical_list: D016588:Anticarcinogenic Agents; D019207:beta Carotene; D014801:Vitamin A