Funding to better understand immune response in colorectal cancer

A new grant from the National Cancer Institute will help researchers with the Genetics and Epidemiology of Colorectal Cancer Consortium, or GECCO, better understand the body’s natural immune response to colorectal cancer and what, exactly, drives it.

Dan Buchanan, Mark Jenkins and team

Pictured: Associate Professor Dan Buchanan (third from left), Professor Mark Jenkins (fourth from left) and team.

The US$3.66 million award will fund a five-year study that could lead to better prevention approaches for this common cancer.

Building on more than a decade of genetic and epidemiological research by the international GECCO team, the new study will weave together many of the biological threads that impact tumor growth and patient survival.

The large, collaborative study will examine how germline genetics, environmental and lifestyle factors, the microbiome and tumor characteristics relate to the profile of T cells in colorectal cancers, and how those T cell profiles relate to cancer survival.

The results of this work may ultimately inform strategies to harness the immune system for the prevention and treatment of colorectal cancer.

Associate Professor Dan Buchanan and Professor Mark Jenkins of the University of Melbourne Centre for Cancer Research, and Professor Roger Milne from the Cancer Council Victoria, are investigators on the grant.

“This is an important international study – the immune system plays a key role in the evolution and progression of colorectal cancer,” said Associate Professor Buchanan.

“Our understanding of the complexity of how T cells respond during tumourigenesis and the factors that drive this response is still limited.

“The results from this work will help us understand the genetic and lifestyle factors that influence the tumour-immune interactions in colorectal cancer and may further the development of immunotherapeutic and immunopreventative strategies.”

The GECCO consortium investigates the various paths to colorectal cancer by following the genetic and biological breadcrumbs that lead to its development.

GECCO’s data coordinating center is housed at the Fred Hutchinson Cancer Research Center and manages the individual-level genetic and epidemiological data of over 130,000 participants from 70 studies across North America, Australia, Asia and Europe.

To date, the researchers have harmonized over 100 lifestyle, environmental, and clinical variables across these studies. They’ve also generated and harmonized over 40 million genetic variants across the genome for each of the 130,000 participants and are currently sequencing the tumor genome for a subset of 7,000 colorectal cancer cases.

“Together with our very committed collaborators, this international consortium has been able to develop a unique resource that does not exist anywhere else in the world,” says Tabitha Harrison, a Hutch genetic epidemiologist and GECCO’s coordinating center manager.

“This provides a powerful resource for addressing important research questions that no single study would be able to undertake alone.”

Among other things, the consortium’s work has led to the development of a risk prediction model to better pinpoint who needs early screening and who doesn’t. They’ve deciphered who might benefit from aspirin, or non-steroidal anti-inflammatory drugs, and who might not. In 2018, GECCO researchers identified 40 new colorectal cancer genetic risk variants, some of which are protective.

“All of this new information helps to inform decisions about interventions, such as screening or chemoprevention, to prevent cancer in healthy people,” said Peters. “This is the path to personalized medicine.”

GECCO investigates genetic variants as well as interactions between genes and lifestyle risk factors that can help promote or prevent colorectal cancer. These include good and bad gene-dietary interactions (i.e., what can happen when you eat vegetables versus red and processed meat) and good and bad gene-environmental interactions that occur as a result of smoking, alcohol use, exercise (or lack thereof), high or low body-mass index and other factors.

For this study, GECCO researchers will analyse data from 2,500 colorectal cancer patients drawn from the world’s leading colorectal cancer cohorts: the Women’s Health Initiative, which also houses its data coordinating center at the Hutch; the Health Professionals Follow-up Study and Nurses’ Health Study, both based at Harvard; the Australian and Ontario sites of the Colon Cancer Family Registry and the Melbourne Collaborative Cohort Study.

The consortium has already completed the germline genotyping and harmonised epidemiologic data for a variety of lifestyle factors and personal characteristics for all of the participating studies.