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Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Is cancer heritable?
- Heritability of cancer
- Identification of BRCA genes
- Heritable component explained
- What is a polygenic risk score?
- What is DNA?
- What is a SNV?
- What is a SNP?
- What is a genotype?
- What is the effect of SNPs?
- Identifying risk SNPs: genetic case control studies
- What is a risk SNP?
- What is the measure of risk?
- Relative risk (RR)
- Multiplicative model
- Progress in identifying common risk alleles
- Heritable component explained
- What are the risks for genotype combinations of multiple SNPs?
- Multiplicative model for 2 SNPs (1)
- Multiplicative model for 2 SNPs (2)
- Interaction between many SNPs
- How many risk alleles does an individual carry?
- Risk allele frequencies, assuming two risk SNPs
- Forming a bell curve distribution
- Implications for risk
- Prevalence of relative risk
- Added complications
- PRS as a weighted sum
- Rescaling the x-axis
- Log relative risk distribution based on known common breast cancer alleles
- Relative risk distribution based on common breast cancer risk alleles
- Other risk factors
- Risk distribution based on common risk alleles and lifestyle factors
- Clinical implications
- The absolute risk of breast cancer in a 40-year-old woman
- Absolute risks of breast cancer
- Absolute risks of breast cancer mortality
- Policy or clinical implications
- Conclusions
- Thank you!
Topics Covered
- The role of inherited genetic variation in cancer risk with a focus on breast cancer
- What is a risk single nucleotide polymorphism (SNP)?
- How multiple risk SNPs combine to affect risk
- The multiplicative model of polygenic risk
- Implications of polygenic risk scores for breast cancer risk prevention in the population
Links
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Talk Citation
Pharoah, P. (2021, January 31). Cancer risk stratification: the role of polygenic risk scores [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 8, 2024, from https://doi.org/10.69645/YUDS5358.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Paul Pharoah has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Introduction to Human Genetics and Genomics
Transcript
Please wait while the transcript is being prepared...
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.