© 1993 by Oxford University Press
Journal of the National Cancer Institute, Vol. 85, No. 18, 1483-1491,
September 15, 1993
© 1993 Oxford University Press
Nutrition Intervention Trials in Linxian, China: Supplementation With Specific Vitamin/Mineral Combinations, Cancer Incidence, and Disease-Specific Mortality in the General Population
National Cancer Institute Bethesda, Md.
Cancer Institute, Chinese Academy of Medical Science Beijing, People's Republic of China
Rutgers University Piscataway, N.J.
Correspondence to: William J. Blot, Ph.D., Biostatistics Branch, Division of Cancer Etiology, National Cancer Institute, 6130 Executive Blvd., Rockville, MD 20852
BACKGROUND: Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardla cancer and a persistently low intake of several micronutrients.
PURPOSE: We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian.
METHODS: Individuals of ages 40–69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 24 factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances.
RESULTS: A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84–0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75–1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64–0.99), with the reduced risk beginning to arise about 1–2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality.
CONCLUSIONS: The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population.
IMPLICATIONS: The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements. [J Natl Cancer Inst 85:1483–1492, 1993]
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S. M. Lippman, P. J. Goodman, E. A. Klein, H. L. Parnes, I. M. Thompson, A. R. Kristal, R. M. Santella, J. L. Probstfield, C. M. Moinpour, D. Albanes, et al. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT) J Natl Cancer Inst, January 19, 2005; 97(2): 94 - 102. [Abstract] [Full Text] [PDF]
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P. R. Taylor and P. Greenwald Nutritional Interventions in Cancer Prevention J. Clin. Oncol., January 10, 2005; 23(2): 333 - 345. [Abstract] [Full Text] [PDF]
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E. R. Miller III, R. Pastor-Barriuso, D. Dalal, R. A. Riemersma, L. J. Appel, and E. Guallar Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality Ann Intern Med, January 4, 2005; 142(1): 37 - 46. [Abstract] [Full Text] [PDF]
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E. R. Greenberg Vitamin E Supplements: Good in Theory, but Is the Theory Good? Ann Intern Med, January 4, 2005; 142(1): 75 - 76. [Full Text] [PDF]
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S. Hercberg The history of {beta}-carotene and cancers: from observational to intervention studies. What lessons can be drawn for future research on polyphenols? Am. J. Clinical Nutrition, January 1, 2005; 81(1): 218S - 222S. [Abstract] [Full Text] [PDF]
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S. A. Savage, C. C. Abnet, S. D. Mark, Y.-L. Qiao, Z.-W. Dong, S. M. Dawsey, P. R. Taylor, and S. J. Chanock Variants of the IL8 and IL8RB Genes and Risk for Gastric Cardia Adenocarcinoma and Esophageal Squamous Cell Carcinoma Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2251 - 2257. [Abstract] [Full Text] [PDF]
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R. H. Liu Potential Synergy of Phytochemicals in Cancer Prevention: Mechanism of Action J. Nutr., December 1, 2004; 134(12): 3479S - 3485S. [Abstract] [Full Text] [PDF]
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S. Hercberg, P. Galan, P. Preziosi, S. Bertrais, L. Mennen, D. Malvy, A.-M. Roussel, A. Favier, and S. Briancon The SU.VI.MAX Study: A Randomized, Placebo-Controlled Trial of the Health Effects of Antioxidant Vitamins and Minerals Arch Intern Med, November 22, 2004; 164(21): 2335 - 2342. [Abstract] [Full Text] [PDF]
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R. S. Eidelman, D. Hollar, P. R. Hebert, G. A. Lamas, and C. H. Hennekens Randomized Trials of Vitamin E in the Treatment and Prevention of Cardiovascular Disease Arch Intern Med, July 26, 2004; 164(14): 1552 - 1556. [Abstract] [Full Text] [PDF]
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D. Li, G. L. Graef, J. A. Yee, and L. Yan Dietary Supplementation with High-Selenium Soy Protein Reduces Pulmonary Metastasis of Melanoma Cells in Mice J. Nutr., June 1, 2004; 134(6): 1536 - 1540. [Abstract] [Full Text] [PDF]
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P. R. Taylor, H. L. Parnes, and S. M. Lippman Science Peels the Onion of Selenium Effects on Prostate Carcinogenesis J Natl Cancer Inst, May 5, 2004; 96(9): 645 - 647. [Full Text] [PDF]
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N. Karunasinghe, J. Ryan, J. Tuckey, J. Masters, M. Jamieson, L. C. Clarke, J. R. Marshall, and L. R. Ferguson DNA Stability and Serum Selenium Levels in a High-Risk Group for Prostate Cancer Cancer Epidemiol. Biomarkers Prev., March 1, 2004; 13(3): 391 - 397. [Abstract] [Full Text]
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W.-Q. Wei, C. C Abnet, Y.-L. Qiao, S. M Dawsey, Z.-W. Dong, X.-D. Sun, J.-H. Fan, E. W Gunter, P. R Taylor, and S. D Mark Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death Am. J. Clinical Nutrition, January 1, 2004; 79(1): 80 - 85. [Abstract] [Full Text] [PDF]
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