Journal of the National Cancer Institute Advance Access originally published online on March 24, 2009
JNCI Journal of the National Cancer Institute 2009 101(7):507-518; doi:10.1093/jnci/djp037
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Total and Cancer Mortality After Supplementation With Vitamins and Minerals: Follow-up of the Linxian General Population Nutrition Intervention Trial
Affiliations of authors: Cancer Institute, Chinese Academy of Medical Sciences, Beijing, Peoples Republic of China (Y-LQ, J-HF, X-DS, Z-WD); Division of Cancer Epidemiology and Genetics, National Cancer Institute (SMD, FK, CCA, MHG, SDM, PRT), and National Center for Complementary and Alternative Medicine (LLJ), National Institutes of Health, Bethesda, MD; Information Management Services, Inc, Silver Spring, MD (BY)
Correspondence to: Philip R. Taylor, MD, ScD, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, Rm 7006, MSC 7236, Bethesda, MD 20892-7236 (e-mail: ptaylor{at}mail.nih.gov).
Background: The General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29 584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with "factor D," a combination of 50 µg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention.
Methods: Participants were assessed by periodic data collection, monthly visits by village health workers, and quarterly review of the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models.
Results: Through May 31, 2001, 276 participants were lost to follow-up; 9727 died, including 3242 from cancer (1515 from esophageal cancer and 1199 from gastric cancer). Participants who received factor D had lower overall mortality (HR = 0.95, 95% CI = 0.91 to 0.99; P = .009; reduction in cumulative mortality from 33.62% to 32.19%) and gastric cancer mortality (HR = 0.89, 95% CI = 0.79 to 1.00; P = .043; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Esophageal cancer deaths between those who did and did not receive factor D were not different overall; however, decreased 17% among participants younger than 55 (HR = 0.83, 95% CI = 0.71 to 0.98; P = .025) but increased 14% among those aged 55 years or older (HR = 1.14, 95% CI = 1.00 to 1.30; P = .47). Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation, with decreased stroke mortality.
Conclusion: The beneficial effects of selenium, vitamin E, and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants. Late effects of other supplementation regimens were also observed.
| CONTEXT AND CAVEATS Prior knowledge The undernourished population of Linxian, China, has high rates of cancer of the esophagus and gastric cardia. In the General Population Nutrition Intervention Trial of 1985–1991, 29 584 Linxian villagers aged 40–69 years were given daily supplements of one or more of four vitamin and mineral combinations. "Factor D," which contained selenium, vitamin E, and beta-carotene, was associated with reduced mortality overall, from cancer, and from gastric cancer. Study design For 15-year follow-up, villagers were interviewed monthly concerning their health and registered cancer deaths were reviewed to look for sustained and delayed effects of the vitamin supplements. Hazard ratios for death by cancer, stroke and other causes were calculated for the four supplement combinations. Contribution Ten years after the end of the trial, participants who took factor D still had a 5% reduction in total mortality and 11% reduction in gastric cancer; these effects were concentrated among participants younger than 55 years. Esophageal cancer decreased 17% in participants younger than 55 years, but increased 14% in those older than 55 years. Implications Sustained benefits were associated with a combination of selenium, vitamin E, and beta-carotene supplementation. More subtle long-term effects were also observed for other vitamin supplements. Limitations It is not known which items in the supplement combination are responsible for the combined effect. Because the study was preformed in a nutritionally deprived population with high rates of esophageal and gastric cancer, the findings might not be applicable to other populations. It is possible that the findings could be biased by a general improvement in nutrition among the participants over the postintervention period. From the Editors
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Manuscript received July 5, 2008; revised January 8, 2009; accepted February 2, 2009.
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