Selenium, selenoenzymes, oxidative stress and risk of neoplastic progression from Barrett's esophagus: results from biomarkers and genetic variants.
Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA) and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX) 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1) concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85). SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR) = 3.95, 95% confidence intervals (CI) = 1.42-10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31-32.58), but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12-0.69). Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1 concentrations with the risk of EA and aneuploidy, which warrants further investigation.
Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Yumie
Y
Takata
Alan R
AR
Kristal
Regina M
RM
Santella
Irena B
IB
King
David J
DJ
Duggan
Johanna W
JW
Lampe
Margaret P
MP
Rayman
Patricia L
PL
Blount
Brian J
BJ
Reid
Thomas L
TL
Vaughan
Ulrike
U
Peters
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D012643:Selenium / Q000378:metabolism*; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D051140:Selenoproteins; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human