Preprint Article Version 1 This version not peer reviewed

Cancer Etiology: Variation in Cancer Risk among Tissues is Poorly Explained by the Number of Gene Mutations

Version 1 : Received: 29 August 2017 / Approved: 30 August 2017 / Online: 30 August 2017 (12:14:52 CEST)

How to cite: Lopez-Lazaro, M. Cancer Etiology: Variation in Cancer Risk among Tissues is Poorly Explained by the Number of Gene Mutations. Preprints 2017, 2017080103 (doi: 10.20944/preprints201708.0103.v1). Lopez-Lazaro, M. Cancer Etiology: Variation in Cancer Risk among Tissues is Poorly Explained by the Number of Gene Mutations. Preprints 2017, 2017080103 (doi: 10.20944/preprints201708.0103.v1).

Abstract

Recent evidence indicates that the risk of being diagnosed with cancer in a tissue is strongly correlated (0.80) with the number of stem cell divisions accumulated by the tissue. Since cell division can generate random mutations during DNA replication, this correlation has been used to propose that cancer is largely caused by the accumulation of unavoidable mutations in driver genes. However, no correlation between the number of gene mutations and cancer risk across tissues has been reported. Because many somatic mutations in cancers originate prior to tumor initiation and the number of cell divisions occurring during tumor growth is similar among tissues, here I use whole genome sequencing information from 22,086 cancer samples and incidence data from the largest cancer registry in each continent to study the relationship between the number of gene mutations and the risk of cancer across 33 tissue types. Results show a weak positive correlation (mean = 0.14) between these two parameters in each of the five cancer registries. The correlation became stronger (mean = 0.50) when gender-related cancers were excluded. Results also show that 1,003 samples from 29 cancer types have zero mutations in genes. These data suggest that cancer etiology can be better explained by the accumulation of stem cell divisions than by the accumulation of gene mutations. Possible mechanisms by which the accumulation of cell divisions in stem cells increases the risk of cancer are discussed.

Subject Areas

stem cells; somatic mutations; cancer prevention; carcinogenesis; whole genome sequencing; stem cell division theory of cancer; bad luck of cancer

Readers' Comments and Ratings (1)

Comment 1
Received: 6 February 2018
Commenter: Miguel Lopez-Lazaro
The commenter has declared there is no conflict of interests.
Comment: This preprint is now accepted for publication in the journal Genes, Chromosomes & Cancer:
http://onlinelibrary.wiley.com/doi/10.1002/gcc.22530/full López-Lázaro, M. (2018), Cancer etiology: Variation in cancer risk among tissues is poorly explained by the number of gene mutations. Genes Chromosomes Cancer. doi:10.1002/gcc.22530
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