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It's clear that rates of early-onset colorectal cancer are on the rise. What's still not clear is why.

Andrew T. Chan, MD, MPH, Director of Epidemiology for the Mass General Cancer Center, and a gastroenterologist focused on cancer prevention among families at high risk of gastrointestinal cancer is working to find out.

Chan is co-leading the global team known as PROSPECT, which received a grant of up to $25m over five years, to study early-onset colorectal cancer from Cancer Grand Challenges after an international competition.

Cancer Grand Challenges is a global funding platform, co-founded by Cancer Research UK and the National Cancer Institute in the US, that supports a community of diverse, global teams to come together, think differently and take on some of cancer’s toughest challenges.

Early-onset colorectal cancer (EOCRC) is an important emerging global problem among individuals younger than 50 years. With Dr. Chan’s leadership, team PROSPECT aims to address this by understanding the pathways, risk factors and molecules involved in its development. The team’s vision is to understand and ultimately try to reverse the network of causal factors throughout the life course that disrupts normal biological processes to promote EOCRC.

We spoke with Dr. Chan to learn more about his work in the PROSPECT team and learn how this award will help accelerate his research.


What Have You Learned in Your Research So Far? 

Although recent decades have seen a decrease in the overall incidence of colorectal cancer, there has been an alarming rise in the number of cases diagnosed in people under 50 years of age, also known as early-onset colorectal cancer (EOCRC) in multiple countries across the world.

Research suggests that this risk is increasing with each new generation and is likely linked to exposures in early life and throughout an individual’s lifetime that are specific to their birth cohort.

Our team has led the field in uncovering contributing causes to this rise in EOCRC, including overweight/obesity, physical inactivity, poor diet (including excessive consumption of sugar-sweetened beverages), and alterations in the gut microbiome.

Despite this progress, these factors do not completely explain the rapid rise in cases, and many unanswered questions remain about the mechanisms responsible for the rise in cases.


With the New Grant, What Do You Hope to Find Out?

Our team has three overarching objectives:

Identify the risk factors associated with EOCRC

We will leverage prospective data from more than 15 diverse human cohorts from across the UK, US, multiple countries in Europe, and Mexico.

We will look at exposure to known risk factors (such as obesity and poor diet) and novel risk factors (including environmental and social factors), as well as features of the gut microbiome that could contribute to EOCRC. These exposures are collectively known as the exposome.

Characterize the underlying mechanisms of causal risk factors

The population data we collect will feed into research to understand how the identified risk factors cause biological changes that increase susceptibility to, or drive the progression of, EOCRC. Insights and hypotheses from human data will be tested in innovative animal models and in vitro organoid models.

By integrating population-based and experimental studies, we also hope to identify at which life stage risk factors begin to play a role in the development of EOCRC.

Develop precision prevention strategies

PROSPECT’s ultimate goal is to identify ways to prevent the development of EOCRC.

The team will set up two types of trials: precision prevention trials (in the US and UK) and community risk assessment trials (in the UK and India) to determine whether knowing EOCRC risk influences people’s motivation to adapt their lifestyles or undergo screening to reduce or prevent this risk.


What Challenges Will You Face?

Although rates of EOCRC are rapidly rising, it still remains a relatively rare event among young people.

So it will be challenging to assemble large enough datasets in which we can identify novel risk factors for the disease. We also believe that many of the risk factors for EOCRC are based on exposures early in life.

To date, there are few studies which have captured detailed information on exposures in childhood and young adulthood. It can also be challenging to motivate younger individuals to participate in research.


Who are Your Collaborators?

Our global team includes 11 investigators from nine institutions in five countries, including: Massachusetts General Hospital, Harvard University, MIT, Broad Institute, Washington University, Institut Pasteur, University of Trento, King’s College London, and BALCO Medical Centre.


How Has Mass General Supported Your Research Throughout the Years?

My career has been devoted to identifying risk factors for gastrointestinal cancers as a means for developing actionable preventive interventions through innovative, multidisciplinary team-science approaches.

In 2017, I was named the Stuart and Suzanne Steele MGH Research Scholar. The MGH Research Scholars program provides researchers with unrestricted funding they need to take their work into new and uncharted territories.


How Does This Award Align with Your Research Goals?

Uncovering the causes of the rising incidence of early-onset colorectal cancer around the globe is a one of the highest priorities in the field. Our research has the potential to uncover the pathways, risk factors and molecules involved in its development which will allow us to ultimately reverse the network of causal factors throughout the life course.

This work will also offer opportunities for preventive interventions that can benefit younger generations. In addition to colorectal cancer, there is a rising incidence of multiple cancer types in young adults.  The research can serve as a model for the study of other early-onset cancers.

This award aligns perfectly with this overarching goal by offering me the requisite resources to tackle one of the most pressing and vexing challenges in cancer research through a disruptive, paradigm-shifting approach.


About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. MGH is a founding member of the Mass General Brigham healthcare system.