title: Inherited Variants in SULT1E1 and Response to Abiraterone Acetate by Men with Metastatic Castration Refractory Prostate Cancer.
abstract: OBJECTIVE
  Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict the response to abiraterone acetate in men with metastatic, castration refractory prostate cancer. The variations may serve as prognostic and predictive biomarkers to allow for more individualized therapy.
  
  
  METHODS
  We evaluated 832 single nucleotide polymorphisms from the OmniExpress genotyping platform (Illumina®) in the boundaries of 61 candidate genes reported to be involved in the androgen metabolic pathway. The purpose was to investigate them for an association with time to treatment failure in 68 white men with metastatic, castration refractory prostate cancer undergoing treatment with abiraterone acetate. Cox proportional hazard analysis was used with Gleason score, age, level of alkaline phosphatase and prostate specific antigen at treatment initiation as covariates. Each single nucleotide polymorphism was assessed using an allele carriage genetic model in which carriage of 1 or more minor alleles contributes to increased risk. Subset analyses were done to determine whether metastasis site, or prior treatment with ketoconazole or docetaxel would interact with the single nucleotide polymorphisms investigated.
  
  
  RESULTS
  Six single nucleotide polymorphisms in the estrogen sulfotransferase gene SULT1E1 were associated with time to treatment failure on abiraterone acetate therapy after false discovery rate (q value) correction for multiple testing while controlling for Gleason score, age, level of alkaline phosphatase and prostate specific antigen at treatment initiation (q <0.05).
  
  
  CONCLUSIONS
  Single nucleotide polymorphisms in SULT1E1 were significantly associated with time to treatment failure in men on abiraterone acetate therapy. The single nucleotide polymorphisms may serve as predictive markers for treatment with abiraterone acetate.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah. Electronic address: neeraj.agarwal@hci.utah.edu.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Anitha B
authors.initials: AB
authors.lastname: Alex
authors.affiliation: Division of Genetic Epidemiology, University of Utah, Salt Lake City, Utah.
authors.forename: James M
authors.initials: JM
authors.lastname: Farnham
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Shiven
authors.initials: S
authors.lastname: Patel
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: David
authors.initials: D
authors.lastname: Gill
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Tyler H
authors.initials: TH
authors.lastname: Buckley
authors.affiliation: Division of Urology, University of Utah, Salt Lake City, Utah.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stephenson
authors.affiliation: Division of Genetic Epidemiology, University of Utah, Salt Lake City, Utah.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cannon-Albright
mesh_terms: D000069501:Abiraterone Acetate / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011110:Polymorphism, Genetic; D017430:Prostate-Specific Antigen; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D012189:Retrospective Studies; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate
keywords: abiraterone; biomarkers; polymorphism, single nucleotide; prostatic neoplasms; treatment failure