The incidence of esophageal adenocarcinoma has been increasing rapidly among many countries. Antioxidant intake is a potentially modifiable protective factor, although the results from individual studies are inconclusive. We conducted a systematic review and statistical synthesis of studies that evaluated the associations between vitamin C, vitamin E, or beta-carotene/vitamin A and the risk of esophageal adenocarcinoma or the adjacent gastric cardia (gastroesophageal junction) adenocarcinoma.
Studies were included if they reported (a) a measure of dietary antioxidant intake; (b) esophageal or cardia adenocarcinoma occurrence; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI), or sufficient data to permit their calculation.
We identified 10 studies (1 cohort, 9 case-control; 1,057 esophageal and 644 cardia cases). Summary estimates stratified by cancer site suggested that higher intakes of vitamin C, beta-carotene/vitamin A, and vitamin E were inversely associated with the risk of esophageal adenocarcinoma (vitamin C, OR 0.49, 95% CI 0.39–0.62, Pheterogeneity = 0.10; beta-carotene, OR 0.46, 95% CI 0.36–0.59, Pheterogeneity = 0.82; vitamin E intake, OR 0.80, 95% CI 0.63–1.03, Pheterogeneity = 0.59). Beta-carotene intake was also inversely associated with the risk of cardia adenocarcinoma (OR 0.57, 95% CI 0.46–0.72, Pheterogeneity = 0.17). Dose effects were observed for most associations.
Pooled results from observational studies suggest that antioxidant intake may be protective against esophageal adenocarcinoma; the data do not support a consistent association between antioxidant intake and the risk of cardia carcinoma. These findings suggest possible etiological differences between these two adjacent malignancies.
1Kaiser Permanente Northern California, Division of Research, Oakland, California; 2Columbia University, New York, New York; and 3Mailman School of Public Health, University of California, San Francisco, Division of Gastroenterology, San Francisco, California
Reprint requests and correspondence: Ai Kubo, M.P.H., Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612.
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CONFLICT OF INTEREST Guarantor of the article: Ai Kubo M.P.H.
Specific author contributions: Both authors (A.K. and D.A.C) have contributed to the reviews of the existing literature, statistical analyses, and the preparation of the manuscript.
Financial support: National Institutes of Health grants K08DK002697, RO1 DK63616, and a Kaiser Permanente Community Benefits Grant.
Potential competing interests: None.
Received February 21, 2007; accepted April 30, 2007.