Other age-related cell and tissue damage that raises the risk of cells becoming cancerous, or reduces the effectiveness of internal-to-the-cell controls that can shut down and destroy cancerous cells, would be the other variable, I'd imagine.
I think far more likely that the predominant variable is the expansion of mutant clones over time to occupy large fractions of the stem cell reservoir.
Possibly so, which is a phenomenon that might explain how stochastic nuclear mutation at its given rates can possibly cause widespread enough harm to be significant. There is an interesting recent paper on that subject:
"Recent single-cell studies point to the possibility that essentially all cells have unshared mutations in their genomes. In view of this extensive genetic diversity, it is perhaps not surprising that mutations that confer a proliferative advantage are readily detected as clonal populations of increasing abundance and size in the elderly. These clonal populations might lead to loss of organismal health through the functional decline of tissue and/or the promotion of disease processes, such as cancer. In this review, we summarize recent research that supports the notion that aberrant clonal expansion (ACE) resulting from cancer-associated mutations are common in noncancerous tissue and accumulate with age. We propose ACE to be a previously underappreciated aging phenotype that is universal in most organisms, affects multiple tissues, and likely helps explain why aging is the biggest risk factor for cancer."
I have shown that in elderly individuals essentially the entire epidermis stem cell compartment, whilst having normal morphology, is occupied by clonally expanded mutant stem cells:-
That sounds very interesting, but after glancing at your figures, I don't see where you make this obvious.
Also, in the intro you say "the risk of skin cancer increases exponentially with age and is associated with accumulation of somatic mutations8". Your source groups ages into only 3 categories... If you look closer at the data you will see that developing most cancers becomes less common in old age (peaks at 60 - 90 years old). For cancers involving tissue like bone or reproductive organs this peaks much earlier, probably due to when the majority of cell divisions are occurring.
