Population dynamics is a cancer driver.

Oliveira, Mariana dos Santos; Griebeler, Marcelo de C; Henz, Bernardo; Santos, Filipe Ferreira dos; Guardia, Gabriela D A; Conceição, Helena B; Galante, Pedro A F; Minussi, Darlan C; Oliveira, Manuel M; Lenz, Guido

Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as the cell turnover rate (CTOR). Despite being in a steady state, tissues have different population dynamics thus producing diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimizes the contribution of ANSEL in cancer growth.

POPULATION dynamics; CELL division; CELL populations; TUMOR growth; STEM cells

Carcinogenesis, 2024, Vol 45, Issue 12, p893

0143-3334

Academic Journal

10.1093/carcin/bgae038