Is accelerated biological ageing behind the rise in early-onset cancers?

Cancer is increasingly recognised as a systemic disease, that interplays with the complex biology of its host. Work from across the Cancer Grand Challenges portfolio and the wider cancer research community is converging on the need to consider the individual as a whole, to truly understand a person's cancer risk. In fact, our latest Cancer Grand Challenges Conference was dedicated to understanding how to leverage host physiology against cancer.

In its latest work, inspired by discussions with the Cancer Grand Challenges community, team PROSPECT set out to understand whether accelerated biological ageing, both systemic and organ-specific, might help explain the troubling rise in early-onset cancers. The team, co-led by Yin Cao and Andrew Chan, is addressing our early-onset challenge, with a specific focus on early-onset colorectal cancer. 

Yin comments, “The rise of multiple early-onset cancers across younger generations suggests there may be common underlying drivers. In addition to identifying individual risk factors, we want to understand how environmental and lifestyle exposures shape the biology of the host and contribute to cancer risk. As a proof of concept, we examined biological ageing as an integrated measure of these cumulative effects.”

First author Riuyi Tian explains, “Biological age reflects how the body is functioning beneath the surface, so two people of the same chronological age can have very different biological profiles.”
 

The team studied 154,169 individuals from the UK biobank and determined biological age using the established PhenoAge algorithm, finding that younger generations appear to be ageing faster biologically. The team went on to validate these findings using other established measures of biological age, as well as in 10,262 individuals from the US All of Us Research Program. The birth cohort effect the team observed reflects the trend seen with the rise of early-onset cancers. And that’s not the only similarity.

Yin explains, “Our findings suggest that accelerated biological ageing is associated with a higher risk of developing multiple cancers earlier in life, specifically early-onset lung cancer, colorectal cancer and uterine cancer.”

The team then looked into organ-specific measures of aging using proteomics approaches, finding links between immune ageing and early-onset lung cancer as well as adipose tissue ageing and early-onset colorectal cancer.

Ruiyi reflects, “Seeing the population data align closely with our biology expectation was a real ‘wow’ moment for the team. The patterns we were observing were not isolated statistical signals, but part of a biologically coherent story.”

Both Yin and Ruiyi caution that the findings need validation, but they have undoubtedly provided the PROSPECT team with a new conceptual framework to think about integrated cancer risk. 

And if validated, the team has uncovered a minimally invasive way to measure the status of the entire body that could be used for early detection, risk-based targeted screening and eventually prevention.

Yin comments, “There will be more work on validation— leveraging existing and under-utilised clinical data— as well as mechanistic understanding, and how we potentially even slow down biological aging in younger populations.”

The team has already benefited from its multi-disciplinary expertise, with its molecular biologists, computational biologists,  cancer biologists, immunologists, and epidemiologists now excited to dig into the mechanisms underlying this phenomenon. And with these findings the team hopes to bring researchers working on aging into the early-onset cancers discussion.

Yin comments, “Cancer Grand Challenges is enabling us to ask fundamentally new questions about the origins of early-onset cancers and accelerate the discovery of risk factors by connecting population-level evidence with biological mechanisms. ”

She continues, “To accelerate discovery, we are piloting a systems-level approach that complements risk factor discovery with an understanding of how cancer risk develops across the life course. Ultimately, we hope this will transform prevention and early detection.”

Written by Rebecca Eccles with thanks to Yin Cao and Ruiyi Tian

Read the paper in Nature Medicine

Learn more about team PROSPECT