Amazing stuff! Cancer is history (soon)!
"Whether mice respond to environmental exposures by developing mutations and cancers strongly depends on their genetic makeup at birth.
Researchers bred four strains of mice with different levels of genetic susceptibility to liver cancer and then exposed them to the same carcinogen. The rate and progression of liver cancer was strongly influenced by the animals’ genetic background. The research might help explain why some people develop cancer when exposed to carcinogens such as cigarette smoke while others don’t."
"... In a study in mice, researchers found that genetic ancestry directly influences how cancer-causing mutations behave and how the resulting cancers grow and interact within the body.
Uncovering why and how cancer behaves in different people is crucial to support the use of personalised medicine, which aims to tailor treatment to a specific patient for better outcomes, experts say. ...
Controlled experiment
To understand the role of genetics, researchers from the universities of Edinburgh, Cambridge, Heidelberg and Yale recreated cancer development under controlled conditions.
Using four genetically distinct groups of mice, representing levels of genetic variation similar to those seen in human populations, the team exposed each group to the same DNA-damaging chemical comparable to those found in some processed meats.
They then tracked how tumours developed in remarkable detail, analysing whole genomes, gene activity, and tumour structure.
Despite identical exposure, the cancers that emerged followed strikingly different paths depending on genetic background. ..."
From the abstract:
"Human cancers are heterogeneous. Dissecting how germline genetic variation and environmental factors shape tumour evolution using human datasets is limited by inherent diversity in genetic backgrounds and environmental exposures.
Here, to overcome these limitations, we re-ran early tumour evolution hundreds of times in diverged inbred mouse strains, generating matched histology and whole-genome and transcriptome sequences.
The sex, environment and carcinogenic exposures were all controlled, and the study design allowed us to capture genetic variation comparable with that observed across human populations while exploiting the nested hierarchical structure of strain–litter–animal–tumour relationships.
Our analyses reveal that epistatic interactions between genetic background and acquired somatic mutations result in population-specific disease progression, including choice of driver mutations, occurrence of whole-genome duplication and subclonal selection dynamics that mirror both cancer susceptibility and tumour growth rate.
Even modest genetic divergence, comparable with that found across human ancestry groups, can strikingly alter selection pressures during cancer development to shape both cancer risk and the trajectory of tumour evolution."
Background genetics and new mutations interact to direct cancer evolution (behind paywall) "Rerunning tumour evolution in mice shows how cancer develops after DNA damage and reveals that background genetics and acquired mutations interact to shape genome stability and selection. This provides experimental evidence that genetic ancestry has an important role in setting the trajectory of cancer evolution."
New clues to long-standing cancer mystery (original news release) "Inherited genetic differences play a crucial role in determining how cancers develop and evolve after DNA damage, a major international study suggests."
Study reveals why DNA damage from smoking and UV rays may cause cancer in some people but not others (original news release) "Scientists have found the first direct evidence of the powerful role our genetic makeup plays in influencing our risk of cancer, with inherited genes interacting with acquired genetic mutations to shape how tumours evolve."
Fig. 1: Cancer susceptibility and mutagenesis are shaped by germline genetic variation.
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