Ornithine decarboxylase G316A genotype is prognostic for colorectal adenoma recurrence and predicts efficacy of aspirin chemoprevention.
OBJECTIVE
The chemopreventive activity of aspirin in colorectal neoplasia may be explained in part by its effect on polyamine metabolism. The ornithine decarboxylase (ODC) G316A polymorphism affects polyamine metabolism through altered expression of ODC. We investigated the influence of ODC G316A on the chemopreventive activity of aspirin in colorectal adenoma (CRA) recurrence.


METHODS
We genotyped ODC G316A in 546 individuals in the United Kingdom Colorectal Adenoma Prevention trial of aspirin for CRA recurrence prevention and pooled our findings with data from two other randomized intervention trials.


RESULTS
The United Kingdom Colorectal Adenoma Prevention participants with homozygous ODC 316AA genotype were at reduced CRA recurrence risk [relative risk (RR), 0.43; 95% confidence interval (95% CI), 0.16-1.15], particularly if also exposed to aspirin (RR, 0.24; 95% CI, 0.03-1.71). In the pooled analysis of 2,207 individuals, those with homozygous ODC 316AA genotype were at significantly reduced CRA recurrence risk (RR, 0.68; 95% CI, 0.47-0.99). Following stratification by genotype and aspirin exposure, individuals with homozygous wild-type or heterozygous genotypes derived modest benefit from aspirin (RR, 0.85; 95% CI, 0.72-1.01), whereas in those with both ODC 316AA genotype and aspirin exposure recurrence risk was halved (RR, 0.52; 95% CI, 0.29-0.91).


CONCLUSIONS
The ODC G316A genotype is prognostic for CRA recurrence and predictive of an enhanced response to aspirin in preventing recurrence. This variant has the potential to be a clinically useful genetic marker to identify individuals likely to derive the greatest benefit from aspirin chemoprevention.
Hubner
Richard A
RA
Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom. Richard.Hubner@icr.ac.uk
Muir
Kenneth R
KR
Liu
Jo-Fen
JF
Logan
Richard F A
RF
Grainge
Matthew J
MJ
Houlston
Richard S
RS
D000236:Adenoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control; D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control; D005260:Female; D017491:Genes, APC; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics*; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011379:Prognosis
D016588:Anticarcinogenic Agents; D009955:Ornithine Decarboxylase; D001241:Aspirin