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The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers

BACKGROUND: It is widely believed that cancers develop upon acquiring a particular number of (epi) mutations in driver genes, but the law governing the kinetics of this process is not known. We have previously shown that the age distribution of incidence for the 20 most prevalent cancers of old age...

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Autores principales: Belikov, Aleksey V., Vyatkin, Alexey, Leonov, Sergey V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351573/
https://www.ncbi.nlm.nih.gov/pubmed/34434669
http://dx.doi.org/10.7717/peerj.11976
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author Belikov, Aleksey V.
Vyatkin, Alexey
Leonov, Sergey V.
author_facet Belikov, Aleksey V.
Vyatkin, Alexey
Leonov, Sergey V.
author_sort Belikov, Aleksey V.
collection PubMed
description BACKGROUND: It is widely believed that cancers develop upon acquiring a particular number of (epi) mutations in driver genes, but the law governing the kinetics of this process is not known. We have previously shown that the age distribution of incidence for the 20 most prevalent cancers of old age is best approximated by the Erlang probability distribution. The Erlang distribution describes the probability of several successive random events occurring by the given time according to the Poisson process, which allows an estimate for the number of critical driver events. METHODS: Here we employ a computational grid search method to find global parameter optima for five probability distributions on the CDC WONDER dataset of the age distribution of childhood and young adulthood cancer incidence. RESULTS: We show that the Erlang distribution is the only classical probability distribution we found that can adequately model the age distribution of incidence for all studied childhood and young adulthood cancers, in addition to cancers of old age. CONCLUSIONS: This suggests that the Poisson process governs driver accumulation at any age and that the Erlang distribution can be used to determine the number of driver events for any cancer type. The Poisson process implies the fundamentally random timing of driver events and their constant average rate. As waiting times for the occurrence of the required number of driver events are counted in decades, and most cells do not live this long, it suggests that driver mutations accumulate silently in the longest-living dividing cells in the body—the stem cells.
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spelling pubmed-83515732021-08-24 The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers Belikov, Aleksey V. Vyatkin, Alexey Leonov, Sergey V. PeerJ Epidemiology BACKGROUND: It is widely believed that cancers develop upon acquiring a particular number of (epi) mutations in driver genes, but the law governing the kinetics of this process is not known. We have previously shown that the age distribution of incidence for the 20 most prevalent cancers of old age is best approximated by the Erlang probability distribution. The Erlang distribution describes the probability of several successive random events occurring by the given time according to the Poisson process, which allows an estimate for the number of critical driver events. METHODS: Here we employ a computational grid search method to find global parameter optima for five probability distributions on the CDC WONDER dataset of the age distribution of childhood and young adulthood cancer incidence. RESULTS: We show that the Erlang distribution is the only classical probability distribution we found that can adequately model the age distribution of incidence for all studied childhood and young adulthood cancers, in addition to cancers of old age. CONCLUSIONS: This suggests that the Poisson process governs driver accumulation at any age and that the Erlang distribution can be used to determine the number of driver events for any cancer type. The Poisson process implies the fundamentally random timing of driver events and their constant average rate. As waiting times for the occurrence of the required number of driver events are counted in decades, and most cells do not live this long, it suggests that driver mutations accumulate silently in the longest-living dividing cells in the body—the stem cells. PeerJ Inc. 2021-08-06 /pmc/articles/PMC8351573/ /pubmed/34434669 http://dx.doi.org/10.7717/peerj.11976 Text en ©2021 Belikov et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Epidemiology
Belikov, Aleksey V.
Vyatkin, Alexey
Leonov, Sergey V.
The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers
title The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers
title_full The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers
title_fullStr The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers
title_full_unstemmed The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers
title_short The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers
title_sort erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers
topic Epidemiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351573/
https://www.ncbi.nlm.nih.gov/pubmed/34434669
http://dx.doi.org/10.7717/peerj.11976
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