I'm David Kerr, professor of cancer medicine at University of Oxford. I have an abiding, lifelong interest in the biology of colorectal cancers, as many of you know. Let's talk a little bit about colorectal cancer in young people.
We have a lad of 14 that we're giving adjuvant chemotherapy to just now, who presented with T4 N2 disease. It's a difficult disease. We've done some additional prognostic tests on the tumor using our digital pathology algorithm, showing, not surprisingly, that it's an aggressive and proved agnostic group. We're going to give him 6 months of treatment with capecitabine and oxaliplatin.
It just made me think again about the, in some ways, remarkable increasing incidence that we're seeing in young adults. By that, I mean individuals who are less than 50 years of age. If we look, for example, at the United States, since the early 1990s, the incidence rate of colorectal cancer in young adults, those under 50, has doubled. It's projected that by the year 2030, using current age population pyramids, that 15% of all new cases of colorectal cancer will be in young adults.
While we're seeing a significant decrease in incidence in older people, we're seeing a completely opposite trend in younger people, and similarly so with mortality. If we look at the mortality in older colorectal cancer patients, it's improving, but it's remaining stagnant in those who are 50 or under.
This is a genuinely puzzling phenomenon. It is one which is being intensely investigated, not surprisingly, just now. In terms of some of the ideas that people have explored, they wouldn't surprise you, such as lifestyle and diet. The other contributing factors are physical inactivity and so on.
Is there anything that is associated with the other risk factors that are genetic? There doesn't seem to be a particularly increased incidence of predisposing conditions, such as family history of colorectal cancer, polyps, or any of the hereditary symptoms that we might expect.
What is interesting, though, is that there is a birth cohort effect. What that means is that when we look at the incidences across the different decades, using data from the United States, the incidence rates are higher in 40-year-old persons born in 1970, at between 24 and 25 per 100,000 of the population, compared with a 40-year-old person born in 1950, with an incidence of only 18 per 100,000 of the population. This pattern becomes even more pronounced in younger generations, including Gen X persons, born between 1965 and 1980, and millennials, born between 1981 and 1996.
Increasing rates across the generations have been noted not only in the United States but also across Europe, Canada, Australia, and Asia. This birth cohort effect, I think clearly demonstrated, suggests that exposures or factors in early life, such as infancy, childhood, and adolescence, could be important determinants of developing colorectal cancer as one grows up and gets older.
To that extent, there was a recent interesting trial reported at ASCO. One of the areas of interest is the gut microbiome and some of the hydrogen sulfide–producing bacteria, like Fusobacterium nucleatum. These are minor bacterial populations in normal people, but they are significantly overrepresented in people with colorectal cancer. These are bacteria, which through the production of hydrogen sulfide, are proinflammatory and procarcinogenic. These could have a role to play in the genesis of early colorectal cancer.
What's interesting is that one of their dominant nutrients is taurine. We know that the most common source of taurine in our diet is these energy drinks that youngsters seem to consume by the gallon. There's some very interesting work coming out, relating possibly that by drinking too many of these energy drinks and oversupplying the gut microflora with taurine, you get overgrowth of these potentially proinflammatory, procarcinogenic germs.
It's an area of intense interest. We've looked at our own genome-wide association studies, and so far, we haven't come up with anything compelling genetically that allows us to identify young people who are particularly at risk of developing colorectal cancer. One could consider whether we should lower the age of inviting people into screening programs. Certainly, in some nations, the age of screening has been lowered to 45 for the sorts of reasons that we've talked about.
We need to think about how we influence lifestyle, how we understand better what these other contributing factors are in early life, and even in utero — what could expectant moms do to reduce those possibilities? Environmental exposures and carcinogens like smoking, alcohol, and so on are all things that one might consider. Lifestyle and diets, such as the Western diet, cause hyperinsulinemia and are sort of procarcinogenic and proinflammatory milieu that might cause colorectal cancer to become more incident and more prevalent in the young.
There is much to consider, but it's a worrying trend that we need to understand better and where we need to consider how we could better intervene. It's definitely a topic of intense research activity at the moment.
I'd be really interested, for those of you who are clinicians, to know whether you have come across increasingly young patients. Do you treat them in the same way that you would older people? What mitigations should we make in the chemotherapy regimens we use? I'd be awfully interested in anything you might have to contribute to the discussion.
As always, thanks very much for listening. I'm very keen to hear any comments or ideas that any Medscapers might have. For the time being, thanks for listening, as always.
https://www.medscape.com/viewarticle/colorectal-cancer-rise-young-adults-2024a1000cta
