Why Are More Young Adults Getting Colorectal Cancer? New Grant Will Support Global Quest to Find Out

Q: What have you learned through 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.

Q: What does team PROSPECT hope to find out as part of this work?

Our team has three overarching objectives:

1. 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.

2. 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.

3. 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.

Q: What challenges are you anticipating?

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

Q: Who are your collaborators?

Our global team includes 11 investigators from 9 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.

Q: 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. This work will 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.

It is critical to put resources behind tackling one of the most pressing and vexing challenges in cancer research through a disruptive, paradigm-shifting approach — and I am grateful for the opportunity to lead the team in doing just that.

Q: 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.