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This talk is about "Colorectal Cancer and
the Rare Variant Hypothesis".
I'll start by explaining the general
nature of cancer, its multistep process.
The genetic changes, the fact that
it's a somatic evolutionary process.
Examples of some changes.
And I'll also be discussing inherited
susceptibilities to colorectal cancer.
And then I'll proceed with saying
something about multifactorial
inheritance and how one can approach
the problems of investigating
multifactorial inheritance to colorectal
cancer and how this can be used for
other types of multifactorial inherited
susceptibility investigations.
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The incidence of colorectal cancer
increases sharply with age, and
this is a characteristic indeed of nearly
all cancers both in humans and animals.
And it's best explained by the fact that
cancers are multistage processes and
we now understand that those multistages,
the different steps that lead to
a cancer are in fact genetic changes and
changes in gene expression
one after another,
occurring until you get
the disease that we call cancer.
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Cancer is therefore a form of somatic
evolution, it's a clonal evolution.
The first mutation gives an advantage
to a cell with respect to potentially
producing a cancer and
then within the clone produced by that
another mutation arises and so on.
Each subsequent mutation giving a further
advantage to the outcome of the cancer.
And in each case the new mutation
has to occur in a clone that carries
all the previous mutations.
There's no possibility of any sexual
exchange between the different
cells that might have different
numbers of mutations.
And our challenge in understanding cancer
is to find what those changes are.
To find out about their functions and
so why they're selected for
and then to use this information in
dealing with cancer as a disease.
