title: Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
abstract: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We, therefore, examined whether presupplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0-7.9 years). Incidence of prostate cancer as a function of plasma α-tocopherol, γ-tocopherol, and supplementation with α-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma γ-tocopherol was not associated with prostate cancer. Men with higher α-tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88-1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44-1.62; P-trend = 0.66]. We found a strong positive plasma α-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29-3.22; P-trend = 0.005]. A positive plasma α-tocopherol-prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7-10; overall Q5 HR, 1.59; 95% CI, 1.13-2.24; P-trend = 0.001; among men receiving selenomethionine, Q5 HR, 2.12; 95% CI, 1.32-3.40; P-trend = 0.0002). Our findings indicate that higher plasma α-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biologic interaction between α-tocopherol and selenium itself or selenomethionine.
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. daa@nih.gov.
authors: Demetrius
authors: D
authors: Albanes
authors: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Cathee
authors: C
authors: Till
authors: Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.
authors: Eric A
authors: EA
authors: Klein
authors: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Phyllis J
authors: PJ
authors: Goodman
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors: Alison M
authors: AM
authors: Mondul
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors: Stephanie J
authors: SJ
authors: Weinstein
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors: Philip R
authors: PR
authors: Taylor
authors: Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
authors: Howard L
authors: HL
authors: Parnes
authors: Massachusetts Veteran's Epidemiology, Research and Information Center, VA Boston Healthcare System, Boston, Massachusetts.
authors: J Michael
authors: JM
authors: Gaziano
authors: Biomarker Laboratory, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Xiaoling
authors: X
authors: Song
authors: Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: Neil E
authors: NE
authors: Fleshner
authors: The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Powel H
authors: PH
authors: Brown
authors: University of California at Irvine, Department of Medicine, Orange, California.
authors: Frank L
authors: FL
authors: Meyskens
authors: Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, Texas.
authors: Ian M
authors: IM
authors: Thompson
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood*; D012307:Risk Factors; D012643:Selenium / Q000097:blood*; D024505:Tocopherols / Q000097:blood*
chemical_list: D012643:Selenium; D024505:Tocopherols