A primer on familial cancer genetics

Published on May 31, 2020   50 min

Other Talks in the Series: Introduction to Human Genetics and Genomics

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Hello, my name is Marc Tischkowitz. I am a Reader in Medical Genetics at the University of Cambridge. And this lecture is an introduction to cancer genetics.
I have no conflicts of interest to disclose.
Learning objectives: so the topics we're gonna cover are an introduction to the principles of cancer genetics. We're going to examine how to make a timely and accurate initial family history assessment. We're going to describe how to confirm cancers and use histology to guide testing for hereditary cancer predisposition. We're gonna look at how to become confident in using communicating risk in cancer genetics. And we're gonna cover some of the common inherited cancers such as breast,
ovarian, and colorectal. So to get going, we are gonna talk a bit about sporadic cancers versus inherited cancers. So this slide shows a copy of a DNA molecule and how it can become mutated.
The original idea of hereditary cancer predisposition was developed by Alfred Knudson. His theory was called a two-hit hypothesis. And his idea was that you have cells divide and divide over a lifetime and you develop one mutation. And then you develop a second mutation over a long period of time. So this could be many decades. And eventually you develop a cancer, once you've got these two mutations. And this shows the cancer developing.
Next slide covers hereditary cancer predisposition. And here you have the egg and the sperm and one or other has a gene mutation. They come together. In this situation, the individual is already born with one copy mutated in every cell in the body. As this is an inherited mutation, the second mutation occurs. But the timeframe for this can be much shorter, because there's already one mutation in all the cells in the body. And again, you would develop normal cells and cancer cells in this situation. And the cancer cells would develop after the second mutation. And because all the cells already have one mutation, the timing for this is much faster than in a sporadic setting. This explains why hereditary cancers due to germline mutations typically occur several decades earlier than sporadic cancers. So if you think about sporadic cancers, two thirds of all cancers occur after the age of 65, which is when most of these sporadic cancers occur. For hereditary cancers, they tend to occur under the age of 50. So they tend to be much earlier.