title: Serum cytokine analysis in a positive chemoprevention trial: selenium, interleukin-2, and an association with squamous preneoplastic disease.
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.
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7232, USA. mr166i@nih.gov
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Roth
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Wei
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
authors.forename: Rachel
authors.initials: R
authors.lastname: Bagni
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Wang
authors.forename: Denise
authors.initials: D
authors.lastname: Whitby
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Dong
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Gail
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.forename: Carol A
authors.initials: CA
authors.lastname: Giffen
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
mesh_terms: D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068579:Celecoxib; D016207:Cytokines / Q000097:blood*; D004938:Esophageal Neoplasms / Q000097:blood* / Q000517:prevention & control; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000097:blood* / Q000517:prevention & control; D016017:Odds Ratio; D011230:Precancerous Conditions / Q000097:blood* / Q000188:drug therapy; D011720:Pyrazoles / Q000627:therapeutic use; D012645:Selenomethionine / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use
chemical_list: D016588:Anticarcinogenic Agents; D016207:Cytokines; D007376:Interleukin-2; D011720:Pyrazoles; D013449:Sulfonamides; D012645:Selenomethionine; D000068579:Celecoxib