Diseases Over Decades: Cancer

I have emphasized time and time again that many of the disease we are fighting in order to live longer and healthier lives initiate their disease process decades before we as humans feel any of the disease symptoms. This is true for cardiovascular disease, insulin resistance and diabetes, dementia, and cancer amongst others.

In this post I would like to share an article published in Nature in 2020 that reiterates this idea specifically with cancer. Not only are the figures visually stunning and data dense, but the message is very clear, cancer is a process that starts decades before we can discover it clinically on imaging, physical exam, or standard blood tests.

To summarize the study, The Evolutionary History of 2,658 Cancers, analyzes whole-genome sequencing data from 2,658 cancers across 38 cancer types to reconstruct the timeline of cancer development. It tracks when key mutations and chromosomal alterations occur, showing that early oncogenesis involves mutations in a limited set of driver genes, while later stages display more genetic diversity and instability. The findings suggest many driver mutations arise years or even decades before diagnosis, highlighting opportunities for earlier detection and intervention​

A direct quote from the article sums it up nicely:

"Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades"

Additionally

"Our study sheds light on the typical timescales of in vivo tumour development, with initial driver events seemingly occurring up to decades before diagnosis, demonstrating how cancer genomes are shaped by a lifelong process of somatic evolution, with fluid boundaries between normal ageing processes and cancer evolution. Nevertheless, the presence of genetic aberrations with such long latency raises hopes that aberrant clones could be detected early, before reaching their full malignant potential."

An interesting factoid: there is a term that comes up on several of the figures "WGD". This refers to "Whole genome duplication", an event where the cancer cell replicates it's entire set of chromosomes, resulting in going from diploid (2 sets of chromosomes) to becoming tetraploid (4 sets of chromosomes). This marks a transition into markedly increased genetic instability and the promotion of cancer progression. It also gives said cancer the ability to 'evolve' more quickly, tolerating more extreme mutations due to a back up copies of genes enabling basic cell function. These 'extreme mutations' likely provide the developing cancer with a distinct 'evolutionary advantage' where the cancer is more likely to evolve mechanisms that allow it to escape the immune system as well as cancer treatments.

The take home from this study is to reiterate that disease processes starts decades before the disease takes hold, so we too must start decades before the disease takes hold to live our fullest and healthiest lives.

I mean, tell me that figure isn't gorgeous!

Cite:

Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S. C., Gonzalez, S., Rosebrock, D., ... & Van Loo, P. (2020). The evolutionary history of 2,658 cancers. Nature, 578(7793), 122-128.

The Evolutionary Histroy of 2658 cancers.pdf

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