title: Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis.
abstract: OBJECTIVE
  Familial adenomatous polyposis because of germline mutation of the adenomatous polyposis coli gene is characterized by development of colorectal adenomas and, ultimately, colorectal cancer. The usefulness of colorectal mucosal compounds to predict the effect on adenoma development of primary chemoprevention with the nonsteroidal anti-inflammatory drug sulindac was evaluated.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled study of 41 subjects genotypically affected with familial adenomatous polyposis but phenotypically unaffected was conducted. Patients received either sulindac or placebo for 48 months, and development of new adenomas was evaluated. The levels of 5 prostanoids, ornithine decarboxylase, and polyamines were measured serially in normal-appearing rectal mucosa.
  
  
  RESULTS
  There were no statistically significant differences between treatment groups in baseline levels of prostanoids, ornithine decarboxylase, or polyamines. At conclusion of the study, 4 of 5 prostaglandin levels were statistically significantly lower in the sulindac group than in the placebo group. Among the subset of patients taking sulindac, 3 of 5 prostaglandin levels were statistically significantly lower in patients who were polyp free than in those who developed polyps. By contrast, there were no statistically significant differences in ornithine decarboxylase or polyamines between treatment groups or in those on sulindac who were polyp free compared with those who developed polyps.
  
  
  CONCLUSIONS
  Colorectal mucosal prostaglandin levels, but not ornithine decarboxylase or polyamines, may be valuable biomarkers to assess appropriate drug dosage and medication compliance in patients undergoing primary chemoprevention therapy with sulindac. Reduction of mucosal prostaglandin levels may be necessary to achieve chemopreventive benefit from this agent.
authors.affiliation: Department of Medicine, and Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Giardiello
authors.forename: Robert A
authors.initials: RA
authors.lastname: Casero
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: Linda M
authors.initials: LM
authors.lastname: Hylind
authors.forename: Jill D
authors.initials: JD
authors.lastname: Trimbath
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Geiman
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Judge
authors.forename: Walter
authors.initials: W
authors.lastname: Hubbard
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Yang
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D003106:Colon / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010641:Phenotype; D011073:Polyamines / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D013467:Sulindac / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D016861:Cyclooxygenase Inhibitors; D011073:Polyamines; D011453:Prostaglandins; D013467:Sulindac; D009955:Ornithine Decarboxylase