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Population dynamics is a cancer driver.

Mariana Dos Santos Oliveira1,2, Marcelo de C Griebeler3, Bernardo Henz4,5

  • 1Departamento de Biofísica, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, 91501-970, Porto Alegre, RS, Brazil.

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Tissue cell turnover rate (CTOR) significantly increases cancer risk by promoting ancestral selection (ANSEL) of mutated cells. High CTOR leads to larger clones and elevated cancer development, independent of mutation load.

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Area of Science:

  • * Evolutionary biology
  • * Cancer research
  • * Tissue dynamics

Background:

  • * Tissues undergo continuous renovation via stem cell division and cell death, known as cell turnover rate (CTOR).
  • * Despite steady states, tissues exhibit diverse population dynamics and clonality levels.
  • * The role of population dynamics as a cancer driver is under investigation.

Purpose of the Study:

  • * To investigate if cell population dynamics, specifically CTOR, can act as a driver of cancer.
  • * To determine the relationship between CTOR, ancestral selection (ANSEL), and cancer risk.

Main Methods:

  • * Utilized the evolutionary software esiCancer to model cell population dynamics.
  • * Simulated CTOR within ranges observed in human tissues.
  • * Analyzed the impact of CTOR on mutation risk and clone expansion.

Main Results:

  • * High CTOR amplifies mutation risk through ancestral selection (ANSEL).
  • * Elevated ANSEL profiles in high CTOR tissues result in few niches of large clones.
  • * CTOR is significantly associated with cancer risk, even after correcting for mutation load.

Conclusions:

  • * Cell population dynamics, particularly CTOR, are significant drivers of cancer.
  • * High CTOR promotes the selection and persistence of mutated cells, increasing cancer risk.
  • * Understanding CTOR's role in ANSEL is crucial for cancer risk assessment and therapeutic development.