Serum cytokine analysis in a positive chemoprevention trial: Selenium, interleukin-2, and an association with squamous preneoplastic disease

Mark J. Roth, Hormuzd A. Katki, Wen Qiang Wei, You Lin Qiao, Rachel Bagni, Guo Qing Wang, Denise Whitby, Zhi Wei Dong, Mitchell H. Gail, Paul John Limburg, Carol A. Giffen, Philip R. Taylor, Sanford M. Dawsey

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Abstract

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 downregulated interleukin (IL)-2 by 9% (P = 0.04), whereas celecoxib downregulated IL-7 by 11% (P = 0.006) and upregulated 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 [odds ratio (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 nonsignificantly 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, whereas 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 in reducing the levels of IL-2.

Original languageEnglish (US)
Pages (from-to)810-817
Number of pages8
JournalCancer Prevention Research
Volume3
Issue number7
DOIs
StatePublished - Jul 2010

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Selenomethionine
Celecoxib
Chemoprevention
Selenium
Interleukin-2
Interleukin-7
Cytokines
Odds Ratio
Serum
Interleukin-13
Down-Regulation
Interleukin-9
Interleukin-11
Interleukin-17
Therapeutics
Randomized Controlled Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Serum cytokine analysis in a positive chemoprevention trial : Selenium, interleukin-2, and an association with squamous preneoplastic disease. / Roth, Mark J.; Katki, Hormuzd A.; Wei, Wen Qiang; Qiao, You Lin; Bagni, Rachel; Wang, Guo Qing; Whitby, Denise; Dong, Zhi Wei; Gail, Mitchell H.; Limburg, Paul John; Giffen, Carol A.; Taylor, Philip R.; Dawsey, Sanford M.

In: Cancer Prevention Research, Vol. 3, No. 7, 07.2010, p. 810-817.

Research output: Contribution to journalArticle

Roth, MJ, Katki, HA, Wei, WQ, Qiao, YL, Bagni, R, Wang, GQ, Whitby, D, Dong, ZW, Gail, MH, Limburg, PJ, Giffen, CA, Taylor, PR & Dawsey, SM 2010, 'Serum cytokine analysis in a positive chemoprevention trial: Selenium, interleukin-2, and an association with squamous preneoplastic disease', Cancer Prevention Research, vol. 3, no. 7, pp. 810-817. https://doi.org/10.1158/1940-6207.CAPR-09-0269
Roth, Mark J. ; Katki, Hormuzd A. ; Wei, Wen Qiang ; Qiao, You Lin ; Bagni, Rachel ; Wang, Guo Qing ; Whitby, Denise ; Dong, Zhi Wei ; Gail, Mitchell H. ; Limburg, Paul John ; Giffen, Carol A. ; Taylor, Philip R. ; Dawsey, Sanford M. / Serum cytokine analysis in a positive chemoprevention trial : Selenium, interleukin-2, and an association with squamous preneoplastic disease. In: Cancer Prevention Research. 2010 ; Vol. 3, No. 7. pp. 810-817.
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abstract = "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 downregulated interleukin (IL)-2 by 9{\%} (P = 0.04), whereas celecoxib downregulated IL-7 by 11{\%} (P = 0.006) and upregulated 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 [odds ratio (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 nonsignificantly 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, whereas 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 in reducing the levels of IL-2.",
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