distinctive from the long-standing “proximal versus
distal colorectum” model has recently been
proposed.33,40 The frequencies of molecular features
such as a high level of microsatellite instability
and extensive CpG island methylation, as
well as BRAF and PIK3CA mutations, appear to
increase continuously from the rectum to ascending
colon.33 Considering a gradual transition of
gut biogeography, the inhibitory effect of aspirin
on cancer may differ according to both the specific
site of the tumor and its molecular features.
Our current study lacked statistical power to examine
effect modification according to both PIK3CA
mutation status and the specific tumor site, and
larger studies should address this question.
Our study has several strengths. We collected
data on aspirin use both before diagnosis and after
diagnosis; this allowed us to examine the potential
influence of the timing of aspirin use in re-