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ESMO 2025 | Challenges in elucidating risk factors and drivers of early-onset CRC
Gianluca Mauri, MD, PhD, University of Milan, Milan, Italy, discusses the challenges of identifying specific risk factors for early onset colorectal cancer (CRC), highlighting the complexity of dissecting the potential interactions between multiple environmental factors. While some studies have implicated colibactin, a genotoxin, as a potential contributor to early onset CRC, this factor only accounts for a subset of cases, leaving many questions unanswered. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
Unfortunately, this is, let’s say, a $1 million question because, I mean, there are still a lot of hypotheses, but still there are very few answers. Indeed, even in our cohort, by focusing on sporadic early onset CRC, we weren’t able to point out specific risk factors. There are several trials, several observational studies that are trying to assess whether environmental factors may be involved, but dissecting which one of the environmental factors can cause actually this epidemic, it’s still an answer, also because there might not be a single factor, but there might be the interaction between more factors that actually are still unknown, unfortunately...
Unfortunately, this is, let’s say, a $1 million question because, I mean, there are still a lot of hypotheses, but still there are very few answers. Indeed, even in our cohort, by focusing on sporadic early onset CRC, we weren’t able to point out specific risk factors. There are several trials, several observational studies that are trying to assess whether environmental factors may be involved, but dissecting which one of the environmental factors can cause actually this epidemic, it’s still an answer, also because there might not be a single factor, but there might be the interaction between more factors that actually are still unknown, unfortunately. However, we think that by profiling and characterizing the biology of these tumors, exploiting omics technologies that are available today. We might go back and see what can cause such kind of, let’s say, scar or signatures that we observe in the patients to come back in, let’s say, in defining the etiology. Today, the only and the most important risk factor, which is being pointed out in a recent Nature paper, was the role of colibactin, which is a genotoxin, which has been demonstrated to be enriched in the early onset CRC population and particularly among those under 40. However, this was reported in 30% of the cases, so there are a lot of cases still to be addressed in terms of what were the causes to drive this increase.
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