title: Serum selenium levels in relation to markers of neoplastic progression among persons with Barrett's esophagus.
abstract: BACKGROUND
  Persons with Barrett's esophagus have a substantially greater risk of esophageal adenocarcinoma than the general population. Higher serum selenium levels have been associated with a reduced risk of several cancers; however, their association with the risk of esophageal adenocarcinoma is unknown. We used a cross-sectional study to investigate the relationship between serum selenium levels and markers of neoplastic progression among persons with Barrett's esophagus.
  
  
  METHODS
  Medical history, blood, and esophageal tissue specimens were collected from 399 members of a cohort study of Barrett's esophagus patients undergoing endoscopic surveillance. Serum selenium levels were measured by flameless atomic absorption spectrophotometry. DNA content of tissue samples was measured by flow cytometry. Loss of heterozygosity (LOH) at 9p and 17p, chromosomal regions which include the p16 and p53 tumor suppressors, respectively, was detected by automated fluorescent genotyping. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided.
  
  
  RESULTS
  Persons with serum selenium levels in the upper three quartiles (i.e., >1.5 micro M) were less likely to have high-grade dysplasia (OR = 0.5, 95% CI = 0.3 to 0.9) or aneuploidy (OR = 0.4, 95% CI = 0.2 to 0.8) than those with levels in the lowest quartile. Serum selenium levels in the upper three quartiles were associated with similar reductions in risk of 17p (p53) LOH (OR = 0.5, 95% CI = 0.2 to 0.9) and increased 4N fraction (OR = 0.6, 95% CI = 0.3 to 1.2). By contrast, serum selenium levels were not associated with 9p (p16) LOH (OR = 1.0, 95% CI = 0.5 to 1.7), a marker that appears early in neoplastic progression.
  
  
  CONCLUSIONS
  Our preliminary results, from a cross-sectional analysis with biologic markers, suggest that higher serum selenium levels may be associated with a reduced risk of esophageal adenocarcinoma among persons with Barrett's esophagus. Because serum selenium was not associated with 9p (p16) LOH, we speculate that selenium may act primarily at later stages of progression toward adenocarcinoma.
authors.affiliation: Cancer Prevention and Trials Program, Fred Hutchinson Cancer Research Center, and Department of Medicine, University of Washington, Seattle 98109-1024 , USA. rrudolph@fhcrc.org
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Rudolph
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.forename: Alan R
authors.initials: AR
authors.lastname: Kristal
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Blount
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Levine
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Galipeau
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Prevo
authors.forename: Carissa A
authors.initials: CA
authors.lastname: Sanchez
authors.forename: Peter S
authors.initials: PS
authors.lastname: Rabinovitch
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reid
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000209:etiology / Q000235:genetics; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D001471:Barrett Esophagus / Q000097:blood* / Q000150:complications*; D014408:Biomarkers, Tumor / Q000097:blood*; D002886:Chromosomes, Human, Pair 17; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000097:blood* / Q000209:etiology / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D016015:Logistic Models; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012307:Risk Factors; D012643:Selenium / Q000097:blood*; D013054:Spectrophotometry, Atomic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000975:Antioxidants; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D012643:Selenium