Sanger Institute scientists share windfall for early bowel cancer research

The grant has been awarded by the European Research Council, which brings together 66 research teams including 239 scientists who will collectively receive a total of €684 million in ERC Synergy Grants.

Colorectal cancer – also known as bowel cancer – can be found anywhere in the large bowel, which includes the colon and rectum. It is the third most commonly diagnosed cancer and accounts for approximately 10 per cent of all cancer cases.

Despite overall colorectal cancer cases decreasing, in the last 20 years there has been a notable increase of early-onset colorectal cancer which is typically defined as receiving a diagnosis below the age of 50 years.

Some countries which have seen this rise include the UK, US, Australia, Japan and multiple European and Latin American countries. If current trends continue, colorectal cancer is projected to become the leading cause of cancer-related deaths among young adults globally by 2030.

The reasons behind this surge in cases have remained a mystery. Young adults diagnosed with colorectal cancer often have no family history of the disease and few known risk factors such as obesity or hypertension. This has fuelled speculation about potential hidden environmental or microbial exposures that are contributing to cases, especially in young adults.

The team at the Sanger Institute has gathered extensive pilot data suggesting that, in recent decades, certain bacteria in infants’ guts that produce mutagens – agents that cause genetic change – have increased the number of DNA mutations in bowel cells early in life. This exposure may help explain the rising rates of early-onset colorectal cancer globally.

With this new grant of €10.4 million and over the course of six years, the team will follow up on previous work which found an association between early onset colorectal cancer and exposure to colibactin – a toxin produced by certain strains of the E. coli bacterium. This work was carried out by Team Mutographs as part of Cancer Grand Challenges, a global research initiative founded by Cancer Research UK and the National Cancer Institute in the US.

The team will collect blood, stool, and colorectal tissue samples from over 3,000 people across 10 countries, including individuals with early and late onset colorectal cancer and healthy controls. They will generate more than 12,000 whole genome sequences from tumour and normal tissue to identify patterned changes in DNA, known as mutational signatures, linked to bacteria that produce genotoxins (DNA-damaging substances).

In parallel, they will screen bacteria for genotoxic activity (damage to DNA such as mutations or breaks) and expose gut organoids – miniature versions of lab-grown organs – to these strains of bacteria to confirm associated changes in DNA. Using advanced computational analysis, the results will help assess the role of bacteria that change or harm DNA in early onset colorectal cancer and inform new prevention strategies.

Ultimately, the researchers hope to reveal new causes of cancer, which may lead to future preventative strategies to help control the incidence of early onset colorectal cancer and the deaths caused by this devastating disease.

Professor Sir Mike Stratton, Senior Group Leader at the Wellcome Sanger Institute, said: “The rise in early onset bowel cancer is one of the most urgent conundrums in modern medicine. This grant will enable us to combine cutting-edge genomic and microbiome research to uncover its causes and ultimately, help develop strategies to prevent it.”

Dr Trevor Lawley, Group Leader at the Wellcome Sanger Institute, said: “We suspect that changes in the bacteria that colonise our guts early in life may be leaving a lasting imprint on our DNA. This grant gives us the opportunity to test this idea on a global scale and understand how microbes may be influencing cancer risk decades later.”

Dr Paul Brennan, Branch Head Genomic Epidemiology at the International Agency for Research on Cancer (IARC) in France, said: “By combining population data with genomic and microbiome research, we hope to uncover how early-life exposures contribute to cancer risk. This collaboration has the potential to change how we think about cancer prevention worldwide.”