How will we do the research?

The overall goal of this project to is to advance our understanding of what causes cancer. We will do this by identifying what factors are creating the distinctive DNA signatures that are associated with cancer.

In order to achieve this goal, we need to find the answers to some important central questions. Different teams across the project will contribute a piece of the puzzle and together we can find the answers we need. This will build the overall picture of the link between DNA signatures and cancer-causing agents.

Why are some cancer types more common in certain areas of the world?

We know that some cancer types are more common in some parts of the world than others. A significant part of the project will be focusing on finding out some of the reasons behind this.

Paul Brennan, International Agency for Research on Cancer (IARC), Lyon, France

Investigating cancer across five continents (Work area 1)

Dr Brennan and his team are coordinating the collection of samples from people affected by cancer from across the world. This is no small task as the project involves over 5,000 participants and we are collecting samples from five continents!

Participating medical teams are collecting samples from people with particular types of cancer who live in areas with high and low risk of each cancer type. By looking at the DNA from cancers from these two groups, the hope is that we can begin to explain why some cancers are much more common in certain areas of the world.

How can we improve the computer programmes that analyse the DNA data?

This project will generate huge amounts of data. We need to develop new computer programmes so we can accurately analyse the data and produce information that it easy for us to interpret.

Ludmil Alexandrov, University of California, San Diego, USA

Developing computer programmes to analyse DNA signatures (Work area 2)

Dr Alexandrov and his team are leading the development of the sophisticated computer programmes that are being used to analyse the huge amount of DNA data being generated by the project. These programmes will be used by all of the other project teams to identify the signatures that cause cancer.

Can we establish a catalogue of the signatures linked to different cancer-causing agents?

We know the causes of some DNA signatures but not others. Looking at DNA from animals and cells grown in the lab can help us to create a catalogue of signatures linked to specific agents. This work will help us to identify new signatures and also back up the findings from the other areas of the project.

Allan Balmain, University of California, San Francisco, USA

How do cancer-causing agents damage DNA in mice? (Work area 3)

Many of the signatures identified so far have no known cause. The team are studying how cancer-causing agents damage DNA in mice and rats by analysing the signatures of DNA damage following exposure.

David Phillips, King’s College London, UK

How do cancer causing agents damage DNA in human cells? (Work area 4)

This team are working with human cells grown in the lab. Recent advancements in this technology means we can grow these cells in three dimensions, forming mini-organs called organoids. These mimic the way our bodies work more closely than the traditional method of growing cells in two dimensions in a dish.
The organoids will be exposed to cancer-causing agents and the team will then examine their DNA. This will allow us to see how these agents cause cancer in humans.

Can we monitor normal cells for warning signs of cancer?

Two teams on the project are working to understand whether DNA signatures can be used as a signal that healthy cells might be more likely to develop cancer. We will see if this information can be used to help identify people at higher risk of cancer.

Peter Campbell, Sanger Institute, Cambridge, UK

Can we identify risk of cancer from normal cells? (Work area 5)

This team are looking at cells from people thought to be at increased risk of cancer. This includes people who smoke, who have been exposed to chemicals such as asbestos or have conditions that can leader to cancer such as liver cirrhosis. These cells will be compared to those from people at lower risk. The team is searching for changes in DNA that could indicate a cell is more likely to become cancerous.

Mike Stratton, Sanger Institute, Cambridge, UK

Can white blood cells be used to monitor exposure to cancer-causing agents? (Work area 6)

This team are investigating whether white blood cells can be used to monitor exposure to cancer-causing agents. White blood cells are part of the body’s immune system and patrol the body in search of bacteria, viruses and other things that cause illness. Because of this, they are likely to be exposed to cancer causing agents.

The team are collecting white blood cells from people exposed to known factors associated with cancer, such as tobacco smoke. They will see if these white blood cells can be used to monitor overall changes to a person’s DNA. If successful, this could ultimately be used to identify and monitor patients at high risk of developing cancer.

All of the work on this project is being developed with people affected by cancer in mind. Our patient advocates, Maggie and Mimi, are working to enhance the impact of our research by making sure the views of patients and the public are taken into account. They are visiting researchers, people affected by cancer and medical centres participating in the project, and are exploring ways of improving the patients’ experiences of cancer research. Their work will also help to influence future research directions.