Data files for simulated advanced adenoma age incidence, under aspirin treatment

Aspirin intake has been shown to lead to significant protection against
colorectal cancer, e.g. with an up to two-fold reduction in colorectal
adenoma incidence rates at higher doses. The mechanisms contributing to
protection are not yet fully understood. While aspirin is an
anti-inflammatory drug and can thus influence the tumor microenvironment,
in vitro and in vivo experiments have recently shown that aspirin can also
have a direct effect on cellular kinetics and fitness. It reduces the rate
of tumor cell division and increases the rate of cell death. The question
arises whether such changes in cellular fitness are sufficient to
significantly contribute to the epidemiologically observed protection. To
investigate this, we constructed a class of mathematical models of in vivo
evolution of advanced adenomas, parameterized it with available estimates,
and calculated population level incidence. Fitting the predictions to age
incidence data revealed that only a model that included colonic crypt
competition can account for the observed age-incidence curve. This model
was then used to predict modified incidence patterns if cellular kinetics
were altered as a result of aspirin treatment. We found that changes in
cellular fitness that were within the experimentally observed ranges could
reduce advanced adenoma incidence by a sufficient amount to account for
age incidence data in aspirin-treated patient cohorts. While the
mechanisms that contribute to the protective effect of aspirin are likely
complex and multi-factorial, our study demonstrates that direct
aspirin-induced changes of tumor cell fitness can significantly contribute
to epidemiologically observed reduced incidence patterns. Data files that
were generated to create predicted advanced adenoma age incidence curves
for virtual patients that received different doses of aspirin for
different decades of their lives. These data files are then processed by
using Mathematica code (Code_Fig4.nb) that is included.