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Background Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. Purpose We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. Methods A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. Results No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). Conclusions Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. Implications While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.

Barrett esophagus, the columnar-lined distal esophagus acquired as a consequence of chronic gastroesophageal reflux, is associated with the development of columnar epithelial dysplasia and esophageal adenocarcinoma. To determine the efficacy of cytopathology in identifying Barrett esophagus and related neoplasia, observations were compared on 150 esophageal cytology samples with concurrent endoscopic biopsy specimens. Sixty-six specimens that contained benign columnar epithelium in either cytologic or biopsy material were identified. Distinctive-type Barrett mucosa with incomplete intestinalization, considered diagnostic of Barrett esophagus, was found in 34 of 66 cases (52%) and was present only in cytologic material in 11 cases. Twenty-two specimens contained cardiac-type mucosa (present only in cytology in ten cases), a finding of uncertain significance due to lack of localization of the sample with respect to the gastroesophageal junction. Fundic-type mucosa was not observed in any specimen. Two cases of distinctive-type Barrett mucosa with columnar epithelial dysplasia were identified in both biopsy and cytology specimens. Among eight Barrett-associated carcinomas (seven adenocarcinomas and one squamous), cytologic material was diagnostic for malignancy in seven and highly suspicious in one. It was concluded that cytopathologic studies are a useful adjunct to biopsy histopathology in the diagnosis of Barrett esophagus and associated carcinoma. The role of cytopathology in the diagnosis of Barrett-related columnar epithelial dysplasia requires further study, and at present a cautious approach with biopsy confirmation is recommended.