title: Selenium- or Vitamin E-Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT.
abstract: Epidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E.
  
  
  
  We undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics.
  
  
  
  We noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome.
  
  
  
  Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks.
  
  
  
  The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050-8. ©2016 AACR.
authors.affiliation: Departments Of Epidemiology & Biostatistics and Urology, University of CA San Francisco.
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
authors.affiliation: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Darke
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Penney
authors.affiliation: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.affiliation: SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Goodman
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA.
authors.forename: Gwo-Shu Mary
authors.initials: GM
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA.
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
authors.forename: Sam
authors.initials: S
authors.lastname: Peisch
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Tinianow
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Cancer Center, Michigan.
authors.forename: James M
authors.initials: JM
authors.lastname: Rae
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.affiliation: The Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston MA.|Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
mesh_terms: D000368:Aged; D001692:Biological Transport / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D012643:Selenium / Q000378:metabolism*; D014810:Vitamin E / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D014810:Vitamin E; D012643:Selenium