CRUK Grand Challenge – Mutographs
International Agency for Research on Cancer (IARC), France & Wellcome Sanger Institute, United Kingdom
United Kingdom, France
The Mutographs research project aims to advance our understanding of the causes of cancer through studies of mutational signatures.
This large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge to address the following main objectives:
- to elucidate the causes of major global differences in cancer incidence through study of mutational signatures;
- to identify and characterize the biological processes underlying mutational signatures and use such signatures to monitor mutagenic exposures in humans.
Different patterns of somatic mutation, "mutational signatures", are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. In the framework of the Mutographs initiative, the International Agency for Research on Cancer is leading the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence.
Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.
Program Goals and Expected Outcomes
The Mutographs project aims to uncover some of the many causes of cancer that remain unknown. In particular, we are exploring why some cancers are very frequent in some parts of the world, but rare in others. This involves searching for tell-tale imprints carved in the genome of 5000 cases of cancer across 5 continents, with different lifestyles and life environments recorded through questionnaires. We expect this study to increase our understanding of what can cause cancer, hence how it can be prevented. This may also help defining who is at risk and may inform cancer early detection and treatment.
What gaps in existing knowledge will be addressed by the study?
While knowledge about the environmental, lifestyle and genetic factors that cause human cancer is increasing, many common cancers exhibit major differences in incidence across the world that we still can’t explain. To address this knowledge gap, the Mutographs study is designed to look across geographical areas of variable cancer incidence, including regions currently under-represented within international genomic initiatives, and link, for the first time at such scale, whole genome profiles together with comprehensive lifestyle/exposure profiles. Through a better understanding of the causes of cancer, this work may lead to new preventive and therapeutic approaches.
Paul Brennan (co-PI, WP1 leader) and Mike Stratton (PI)
University of California, San Diego
University of California, San Francisco
King’s College London, United Kingdom
Wellcome Sanger Institute
Pancreatic Cancer Research Fund