The explanation for the contrast in results between the
PHS and WHS incidence data with the findings from these
2 metaanalyses is unclear. First, both the PHS and WHS
studies used alternate-day dosing regimens, in contrast to
the daily dosing used in the studies included by Rothwell
and colleagues. It is possible that alternate-day dosing may
be less effective than daily dosing in inhibiting carcinogenesis.
Second, the duration of follow-up in both the PHS
and WHS studies may have been insufficient to detect a
difference in CRC incidence. In their metaanalysis determining
CRC incidence (16), Rothwell and colleagues noted
at least a 7-year delay after initiation of aspirin treatment
before a reduction in CRC incidence even began to emerge
(Fig. 1), with a clear reduction not evident until after 10
years. Thus, it is possible that longer follow-up of the WHS
or PHS may show a potential protective benefit. Third, in
the WHS, the equivalent daily dose of aspirin was 50 mg,
lower than the 75 mg/d shown to be effective in both
metaanalyses.