Abstract
Objectives: The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics.
Methods: Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models.
Results: 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9–1.0); prostate (RR = 1.0, 95% CI = 0.9–1.1); colon (RR = 0.9, 95% CI = 0.7–1.2); or lung (RR = 0.9, 95% CI = 0.7–1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7–1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8–1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7–1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6–1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3–0.8).
Conclusions: The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.
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References
Peto R, Doll R, Buckley JD, Sporn MB (1981) Can dietary beta-carotene materially reduce human cancer rates? Nature 290: 201–208.
Burton GW, Ingold KU (1984) Beta-carotene: an unusual type of lipid antioxidant. Science 224: 569–573.
Manson JE, Jonas MA, Hunter DJ, Buring JE, Hennekens CH (1993) Prospective cohort studies of vitamins and cancer. In: Bray GA, Ryan DH, eds. Vitamins and Cancer Prevention. Pennington Center Nutrition Series, Vol. 3. Baton Rouge, LA: Louisiana University Press, pp 87–109.
Van Poppel G (1996) Epidemiologic evidence for β-carotene in prevention of cancer and cardiovascular disease. Eur J Clin Nutr 50(Suppl. 3): S57–S61.
Alpha-Tocopherol, Beta-Carotene Prevention Study Group (1994) The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330: 1029–1035.
Omenn GS, Goodman GE, Thornquist MD, et al. (1996) Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334: 1150–1155.
Blot WJ, Li J-Y, Taylor PR, et al. (1993) Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/ mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 85: 1483–1492.
Hennekens CH, Buring JE, Manson JE, et al. (1996) Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334: 1145–1149.
Lee I-M, Cook NR, Manson JE, Buring JE, Hennekens CH (1999) Beta carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst 91: 2102–2106.
Albanes D, Heinonen OP, Taylor PR, et al. (1996) α-Tocopherol and β-carotene supplements and lung cancer incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: effects of base-line characteristics and study compliance. J Natl Cancer Inst 88: 1560–1570.
Omenn GS, Goodman GE, Thornquist MD, et al. (1996) Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 88: 1550–1559.
Taylor Mayne S, Handelman GJ, Beecher G (1996) β-Carotene and lung cancer promotion in heavy smokers-a plausible relationship? J Natl Cancer Inst 88: 1513–1515.
Steering Committee of the Physicians' Health Study Research Group (1989) Final report on the aspirin component of the ongoing Physicians' Health Study. N Engl J Med 321: 129–135.
Manson JE, Buring JE, Satterfield S, Hennekens CH (1991) Baseline characteristics of participants in the Physicians' Health Study: a randomized trial of aspirin and beta-carotene in U.S. physicians. Am J Prev Med 7: 150–154.
Mettlin C, Graham S (1979) Dietary risk factors in human bladder cancer. Am J Epidemiol 110: 255–263.
La Vecchia C, Negri E, Decarli A, D'Avanzo B, Liberati C, Franceschi S (1989) Dietary factors in the risk of bladder cancer. Nutr Cancer 12: 93–101.
Shibata A, Paganini-Hill A, Ross RK, Henderson BE (1992) Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer 66: 673–679.
Michaud DS, Spiegelman D, Clinton SK, Rimm EB, Willett WC, Giovannucci EL (1999) Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J Natl Cancer Inst 91: 605–613.
D'Avanzo B, Ron E, La Vecchia C, Franceschi S, Negri E, Ziegler R (1997) Selected micronutrient intake and thyroid carcinoma risk. Cancer 79: 2186–2192.
Franceschi S, Levi F, Negri E, Fassima A, La Vecchia C (1991) Diet and thyroid cancer: a pooled analysis of four European case-control studies. Int J Cancer 48: 395–398.
Heinonen OP, Albanes D, Virtamo J, et al. (1998) Prostate cancer and supplementation with α-tocopherol and β-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 90: 440–446.
Satterfield S, Greco PJ, Goldhaber SZ, et al. (1990) Biochemical markers of compliance in the Physicians' Health Study. Am J Prev Med 6: 290–294.
Cook NR, Stampfer MJ, Ma J, et al. (1999) Beta-carotene supplementation of low baseline levels and decreased risk of total and prostate cancer. Cancer 86: 1783–1792.
McLarty JW, Holiday DB, Girard WM, Yanagihara RH, Kummet TD, Greenberg SD (1995) Beta-carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study. Am J Clin Nutr 62: 1431S-1438S.
Fukao A, Tsubobo Y, Kawamura M, et al. (1996) The independent association of smoking and drinking with serum beta-carotene levels among males in Miyagi, Japan. Int J Epidemiol 25: 300–336.
Kitamura Y, Tanaka K, Kiyohara C, et al. (1997) Relationship of alcohol use, physical activity and dietary habits with serum carotenoids, retinol and alpha-tocopherol among male Japanese smokers. Int J Epidemiol 26: 307–314.
Albanes D, Virtamo J, Taylor PR, Rautatahti M, Pietinen P, Heinonen OP (1997) Effects of supplemental beta-carotene, cigarette smoking, and alcohol consumption on serum carotenoids in the Alpha-Tocopherol, Beta-Carotene Prevention Study. Am J Clin Nutr 66: 366–372.
Forman MR, Beecher GR, Lanza E, et al. (1995) Effect of alcohol consumption on plasma carotenoid concentrations in premenopausal women: a controlled dietary study. Am J Clin Nutr 62: 131–135.
Ahmed S, Leo MA, Lieber CS (1994) Interactions between alcohol and beta-carotene in patients with alcoholic liver disease. Am J Clin Nutr 60: 430–436.
Glynn SA, Albanes D, Pietinen P, et al. (1996) Alcohol consumption and risk of colorectal cancer in a cohort of Finnish men. Cancer Causes Control 7: 214–223.
Enger SM, Longnecker MP, Chen MJ, et al. (1996) Dietary intake of specific carotenoids and vitamins A, C, and E, and prevalence of colorectal adenomas. Cancer Epidemiol Biomarkers Prev 5: 147–153.
Tavani A, Ferraroni M, Mexxetti M, Franceschi S, Lo Re A, La Vecchia C (1998) Alcohol intake and risk of cancers of the colon and rectum. Nutr Cancer 30: 213–219.
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Cook, N.R., Lee, IM., Manson, J.E. et al. Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States). Cancer Causes Control 11, 617–626 (2000). https://doi.org/10.1023/A:1008995430664
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DOI: https://doi.org/10.1023/A:1008995430664