title: Ornithine decarboxylase polymorphism modification of response to aspirin treatment for colorectal adenoma prevention.
abstract: BACKGROUND
  Previous research suggests that the G315A single-nucleotide polymorphism in the ornithine decarboxylase (ODC) gene may be a genetic marker for risk of colorectal neoplasia and may also modify the association of aspirin use with risk.
  
  
  METHODS
  We tested these hypotheses among participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to placebo or to aspirin treatment (81 or 325 mg daily) and followed for 3 years for the occurrence of new adenomas. Genomic DNA from 973 subjects was analyzed for ODC genotype. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to test the association between ODC genotype and adenoma occurrence and interactions with aspirin treatment. All statistical tests were two-sided.
  
  
  RESULTS
  Of the 973 subjects, 54% were homozygous wild-type (GG), 7% were homozygous variant (AA), and 39% were heterozygous individuals; the allele frequencies varied statistically significantly by race and ethnicity. Among these subjects, the absolute risk of any adenoma was 45% and the risk of an advanced lesion was 10%. Overall, no association was found between ODC genotype and the occurrence of new adenomas, but genotype did modify the effect of aspirin on adenoma risk. Although aspirin treatment had no protective effect among subjects with a GG genotype, among subjects with at least one A allele, it was associated with statistically significant reduced risks of any adenoma (RR = 0.77, 95% CI = 0.63 to 0.95; P = .02, P(interaction) = .04) and of advanced lesions (RR = 0.51, 95% CI = 0.29 to 0.90; P = .02, P(interaction) = .02). Among subjects with at least one A allele, 40.8% who took aspirin versus 52.9% who took placebo developed adenomas; 7.1% versus 14.0% developed advanced lesions.
  
  
  CONCLUSIONS
  ODC genotype may modify the response to aspirin treatment for colorectal adenoma prevention.
authors.affiliation: Department of Community and Family Medicine, Dartmouth Medical School, 46 Centerra Parkway, Ste. 300, Lebanon, NH 03766, USA. elizabeth.l.barry@dartmouth.edu
authors.forename: Elizabeth L R
authors.initials: EL
authors.lastname: Barry
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Shubha
authors.initials: S
authors.lastname: Bhat
authors.forename: Maria V
authors.initials: MV
authors.lastname: Grau
authors.forename: Carol A
authors.initials: CA
authors.lastname: Burke
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Ahnen
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Thomas G
authors.initials: TG
authors.lastname: O'Brien
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000208:ethnology / Q000235:genetics / Q000517:prevention & control*; D011125:Adenomatous Polyposis Coli / Q000188:drug therapy; D000368:Aged; D000409:Alanine; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D005787:Gene Frequency; D005838:Genotype; D005998:Glycine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009955:Ornithine Decarboxylase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment
chemical_list: D016588:Anticarcinogenic Agents; D005765:Gastrointestinal Agents; D005492:Folic Acid; D009955:Ornithine Decarboxylase; D000409:Alanine; D001241:Aspirin; D005998:Glycine