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1.  Serum cytokine analysis in a positive chemoprevention trial: Selenium, Interleukin-2 and an association with squamous preneoplastic disease 
This study represents a multiplex cytokine analysis of serum from a 10-month randomized, controlled trial of 238 subjects that investigated the effects of selenomethionine and/or celecoxib in subjects with mild or moderate esophageal squamous dysplasia. The original chemoprevention study found that among those with mild dysplasia, selenomethionine treatment favorably altered dysplasia grade. The current analysis found that selenomethionine down-regulated IL-2 by 9% (p=0.04), while celecoxib down-regulated IL-7 by 11% (p=0.006) and up-regulated IL-13 by 17% (p=0.008). In addition, an increase in IL-7 tertile from baseline to t10 was significantly associated with an increase in dysplasia grade, both overall (OR=1.47, p=0.03) and among those with mild dysplasia at t0 (OR=2.53 p=0.001). An increase in IL-2 tertile from baseline to t10 was also non-significantly associated with worsening dysplasia for all participants (OR=1.32 p=0.098), and significantly associated with worsening dysplasia among those with mild dysplasia at baseline (OR=2.0 p=0.01). The association of increased IL-2 with worsening dysplasia remained significant in those on selenomethionine treatment who began the trial with mild dysplasia (OR=2.52 p=0.03). The current study shows that selenomethionine supplementation decreased serum IL-2 levels, while celecoxib treatment decreased IL-7 levels and increased IL-13 levels during a 10 month randomized chemoprevention trial. An increase in IL-2 or IL-7 was associated with increased severity of dysplasia over the course of the trial, especially in those who began the trial with mild dysplasia. The favorable effect of selenomethionine on esophageal dysplasia in the original trial may have been mediated in part by its effect on reducing levels of IL-2.
doi:10.1158/1940-6207.CAPR-09-0269
PMCID: PMC2900463  PMID: 20587703
chemoprevention; interleukin-2; preneoplasia; gastrointestinal tract; selenium
2.  Total and Cancer Mortality After Supplementation With Vitamins and Minerals: Follow-up of the Linxian General Population Nutrition Intervention Trial 
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.
doi:10.1093/jnci/djp037
PMCID: PMC2664089  PMID: 19318634

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