According to Knudson hypothesis, cancer mutations accumulate in order. Statistics says, that cancer probability increases as sixth order of age, which may mean six consequential steps to cancer.
But, mutations are random in nature. There is no apparent cause, why mutations ABCDEF can't occur in reverse order, i.e. FEDCBA and any other possible orders.
If unordered, any number of required mutations should cause flat age dependency.
Hence, something is ordering these mutations, i.e. making mutation B impossible until A occurs and so on.
What is it?
UPDATE
Cancer incidence dependency on age:
The graph is not linear, which means that mutations are not independent.
UPDATE 2
Let's regard some cancer, which requires 6 mutations. It's incidence distribution should be like shown above.
Now suppose we knew the distribution of all precancer stages, i.e. the distribution of people with 1, 2, 3 and so on mutations. These distributions should look similar to final distribution
Now let's regard only one (first) mutation.
Why is it's incidence age dependent?
Mutations are random. They should not depend on age. If they do depend on age, then they are not random. If "they" are not random, then "they" are not mutations.
Or, in other words, the cause of progression is not a mutation itself.
Isn't it true?
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