Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures

Abstract

Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting.

Machine Learning: A New Prospect in Multi-Omics Data Analysis of Cancer

“…Conversely, different factors related to an individual's lifestyle such as diet, obesity, and some viral infections or environmental agents like exposure to chemicals and hazardous radiations can be classified as exogenous risk factors (Wu et al, 2018). All of these categories and more on can play a key role in initiation of carcinogenesis multistep process by occurrence of genetic mutations and epigenetic alterations (Belizário, 2018;Sheikh-Hosseini et al, 2021). In other words, the epigenome and the genome can have mutual interaction in the onset of cancer.…”

Insights into breast cancer phenotying through molecular omics approaches and therapy response

“…Cancer is defined as genetic disease and is molecularly characterized by accumulation of mutations and epimutations that lead to functional dysregulation of cell genome and epigenome-driven processes [1] .…”

“…Cancer is defined as genetic disease and is molecularly characterized by accumulation of mutations and epimutations that lead to functional dysregulation of cell genome and epigenome-driven processes [ 1 ] . Nonetheless, different genetic and epigenetic variations within patients to patients can lead to a same disease phenotype, e.g., uncontrolled cell growth.…”

“…Epigenetic alterations participate in all steps of cancer, from tumor initiation to cancer progression and metastasis [ 1 , 12 ] . It is now well understood that both losses and gains of DNA methylation occurring in CpGs motifs, as well as aberrant chromatin organization, contribute significantly to cancer associated phenotypes [ 12 ] .…”

bad mathematics of the bad luck theory

“…Thus each model has to pass a thorough examination until one can decide to trust it. Nevertheless some cancer specialists ( [1,6,14,21]) just believe that the Bad Luck theory is right and use it as a basis for the further research. The purpose of this paper is to stop that common misconception by demonstrating the crucial mathematical mistakes in the theory.…”