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0:00
Hello, my name is Professor Paul Pharoah from
the Centre for Cancer Genetic Epidemiology at the University of Cambridge.
Today, I'm going to be talking about how we can use polygenic risk scores to stratify
individuals according to their risk of
cancer, and potentially to use that in preventing cancer.
0:20
I'm first going to be saying a little bit about the evidence that
cancer can be inherited and tends to run in families,
then I'm going to be talking about
single-nucleotide polymorphisms (or SNPs) and how they contribute to
cancer risk with a particular emphasis on how we estimate risks for combinations of SNPs,
the so-called 'multiplicative model' or polygenic risk.
Finally, I'm going to talk about the implications specifically for breast cancer risk.
Throughout this talk I'm primarily talking about breast cancer,
although much of what I say could equally be applied to any other cancer.
0:59
The first question to answer is,
can cancer be inherited or is it heritable?
There are huge amounts of data that tell us that
somebody who has a close relative diagnosed
with a specific cancer is at an increased risk of developing the same cancer themselves.
For example, a woman who has a first-degree relative
(a mother or a sister) who had breast cancer
is at an approximately two-fold increased risk herself.
There have been very large twin studies that show most of
this excess familial risk (or heritable risk) is due to shared genetic makeup.
However, shared lifestyle environment also contributes slightly.
1:39
It has been recognised for many years that cancer tends to run in families.
Indeed in 1866, in Paul Broca's classic book 'Traité des Tumeurs',
in the middle of the book this pedigree,
which is shown on the right-hand side of the page, is described.
In this pedigree there are three generations of a single family, in which
several women in each generation developed
either breast cancer or liver cancer at a very early age.
It's likely that the cases of liver cancer presented secondary cancers,
and it could well be that this was a family history caused by
a mutation in one of the genes such as BRCA1 and BRCA2.
