Shortly after my 54th birthday, I received a package. The enclosed instructions told me that next time I emptied my bowels, I should scrape a bit of the stool into a small sample bottle, seal it in a pre-paid envelope and drop it into the post. I did the deed and, a few weeks later, was invited to hospital. My sample contained blood; a colonoscopy was ordered to rule out colorectal cancer.
I don’t, thankfully, have colorectal cancer, and a colonoscopy at 54 is a classic initiation into middle age. But in the coming years, this particular rite of passage might start happening much earlier. While rates of this cancer among people in my age group have been declining thanks to screening programmes like these, the story for the under-50s is far more troubling.
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From being virtually unheard of in the 20th century, early-onset colorectal cancer (EOCRC), as it is called in people under 50, now accounts for around . That number is predicted to more than double by 2030, and by then, EOCRC is expected to be the most common form of fatal cancer in Americans aged 20 to 49.
The reason why is uncertain, but an ambitious new project is exploring potential causes – as well as the idea that EOCRC may be a distinct and more aggressive form of the disease. Meanwhile, as routine screening is extended to younger groups – in January, England lowered its screening age to 50 – and new, less-invasive tests get approved, there is hope the worst prognoses can be avoided.
Colorectal cancer is an umbrella term for cancers of the large intestine and rectum. In 2022, the year for which the most recent figures are available, there were around , making CRC the third most common cancer after those of the lung and female breast. More than 900,000 people died from it that same year, reflecting its lethality – despite advances in treatment, it .
The rise of EOCRC was , in an analysis of cancer statistics collected between 1973 and 1999 in the US. This revealed that in people aged 60 and over, colon cancer rates were stable and rectal cancer rates falling, in part due to more active screening programmes. “Colorectal cancer screening certainly has been a success story,” says , a gastrointestinal cancer specialist at Massachusetts General Hospital in Boston.
But the analysis also found that among 20 to 40-year-olds, both types of cancer were rising, with rectal cancer up by 75 per cent. Both were still much less common in younger people overall, the researchers noted, but there was a clear trend. Similar increases were soon discovered in many higher-income countries, including Australia, New Zealand, Canada and the UK, and the rise continues to this day. In the US, colorectal cancer is now the leading cause of cancer deaths among men under 50, and the second-leading among women under 50, up from being the fourth-leading cause of cancer deaths in the late 1990s.
Generation effect
But growing rates of EOCRC are no longer confined to these economies. The most recent analysis combed through data from 50 countries and territories and found that this is ; the list now includes some middle-income nations such as Belarus, Ecuador and Turkey.
“It’s confirmation of what we already knew, that the rates are rising across many countries, more so in higher economically developed countries, but also increasingly in middle-income as well,” says cancer diagnostics researcher at the University of Exeter, UK, who wasn’t an author on the paper. The annual global growth rate of new diagnoses in the under-50s varies from about 1 per cent to 4 per cent, according to the , with the . The rise is unlikely to be an artefact of better diagnosis, says Bailey. “I think it is a real effect and not just that we’re picking up more cases.”
The growth is an illustration of what is known as the birth cohort effect, according to at Harvard Medical School. Each successive generation has a higher risk of developing the disease than older cohorts had at the same age. In the US, for example, have roughly double the risk of developing colon cancer and quadruple the risk of developing rectal cancer throughout their lifetime as those born in 1950 (see graph).
For EOCRC, the birth cohort effect began in people born around 1960, supporting the idea that the rise might be related to , says Giannakis. Additionally, though a significant portion of cases seem to , the majority of recent ones are “sporadic”. These aren’t related to genetic predisposition, but rather are linked to lifestyle or environmental factors.
Potential triggers
But what factors exactly? From the 1950s, people in the parts of the world that have witnessed this rise experienced that altered their environmental exposures, points out , a gastrointestinal oncology researcher at Erasmus University Medical Center in Rotterdam, the Netherlands. People began consuming more highly processed, low-fibre foods, red meats and alcohol, while also sitting more and moving less. Alongside this came an increase in obesity and conditions such as type 2 diabetes.
At the same time, the use of antibiotics soared. Antibiotics can have a profound impact on the gut microbiome, and there is good evidence that at any age. So are such as ulcerative colitis and Crohn’s disease, which have also risen dramatically in young people, probably as a result of similar environmental changes.
All of these and more have been suggested as potential causes of the EOCRC surge. But despite years of research, “it’s not fully understood why rates are rising so rapidly in this age group”, says Bailey. The strongest evidence is that are risk factors, according to a recent review led by at the University of Manchester, UK. But research on other potential triggers has produced . For example, some findings show a link between heavy consumption of processed meat and EOCRC, but others don’t; similar research on red meat, alcohol, smoking, lack of physical activity, antibiotics and low intake of fruit, vegetables and fibre has also proven inconclusive.
Last year, the Cancer Grand Challenges initiative set up a five-year , with the aim of finally nailing down the risk factors, understanding the mechanisms by which they cause the disease and eventually coming up with new treatments and dietary interventions.
The project will initially try to drill down into the precise role of the usual suspects such as alcohol, processed foods and obesity. With alcohol, for example, it may be that certain patterns of drinking are riskier than others. “There may be differential associations between drinking with a meal versus binge drinking,” says Chan, who is co-leader of the project. “We’d like to really focus on the nuance of these exposures because, ultimately, it may be more complex than just simply, ‘I’ve been exposed’. It’s ‘how was I exposed and in what context?'”
The project will also go in search of previously unknown causal agents. “We’re motivated to identify new risk factors, particularly new risk factors that may have a specific effect on younger individuals. We don’t want to overlook factors because they haven’t been previously considered,” says Chan. Some of those include microplastics and certain ingredients of ultra-processed foods, such as emulsifiers and preservatives.
Another critical research question concerns the possibility that EOCRC may not be the same as late-onset colorectal cancer (LOCRC), but a distinct disease that would require a different treatment strategy. This idea was first floated in 2017, when a team led by at Weill Cornell Medicine in New York compared the characteristics of hundreds of thousands of CRC cases from the under and over-50s. Shah’s team used genetic analysis to determine that the two cancers are “clinically, pathologically, and molecularly” distinct.
Since then, more work has uncovered other differences. The vast majority of LOCRCs are a type of cancer called an adenocarcinoma, which starts in mucus-producing cells, with just a handful being another type, , which start in cells in the endocrine and nervous systems and can impact hormone production. But when a team led by at Rutgers New Jersey Medical School looked at all the EOCRC cases recorded in the US from 2011 to 2020, it found that the rate of increase of neuroendocrine tumours was greater than that of adenocarcinoma among the EOCRC cases. At the moment, this remains an empirical observation, but it adds to the evidence that EOCRC is often distinct from LOCRC.
There's still a perception that young people are too young to get colorectal cancer
EOCRC also tends to be diagnosed at a more advanced stage, . This could be owing to several factors: a lack of screening might delay diagnosis until the cancer is more advanced, when symptoms typically appear, while symptomatic people under the age of 50 typically experience , often because of mistaken initial diagnoses. But studies have also suggested that EOCRC is simply more aggressive.
Another difference is that while LOCRC tends to be found on the right side of the bowel, EOCRC clusters on the left side. Left and right-sided colorectal tumours are derived from different types of tissue; around and these patients have a worse prognosis. The current thinking, says Bailey, is that left-sided tumours are caused by environmental carcinogens that act relatively quickly, hence their preponderance in younger adults. But, says Chan, “that work is still very much under way, and it needs to be an area of focus”.
Low screening uptake
While we wait for definitive answers, what can be done to stem the rising tide? Earlier screening would help, says Bailey. But simply offering screening to younger cohorts is no cure-all. In 2018, the American Cancer Society recommended that the age to start routine screening should be in order to reach ; the followed suit in 2021. However, uptake has been low. In 2021, the most recent year for which figures are available, fewer than 20 per cent of eligible adults aged 45 to 49 were up to date on their screening.
That is somewhat unsurprising. Standard screening methods carry a considerable ick factor, not to mention discomfort, that can . Screening also carries risks, says Bailey. Most positive faecal tests, which measure the amount of haemoglobin, a protein in red blood cells, in the stool, are false alarms – but that can only be confirmed via a colonoscopy. This can be either a full colonoscopy or a partial version, known as a sigmoidoscopy, that examines only the lowest part of the bowel, or a computed tomography colonography, in which the colon is inflated so a scanner can look for signs of cancer.
Colonoscopies – believe me – aren’t enjoyable, but they can also cause bleeding and come with a risk, though low, of a perforated bowel. There is also the psychological stress of being told you may have cancer. Because of these factors and others – including hospitals’ finite capacity for performing colonoscopies – deciding on an ideal age to start screening is difficult, says Bailey.
New blood tests may solve some of these problems. The first, Colo91ɫƬ, which looks for DNA markers of CRC in the blood, was , and another, Shield, followed last year. More are in development. A found that offering the blood test to adults who were overdue for a CRC check increased the overall uptake of screening.
Neither of the approved tests, however, are in detecting EOCRC; moreover, people who test positive will still need a colonoscopy. Colonoscopy screening also has the added advantage of being a preventative measure, according to at Stanford University in California. While examining the colon, doctors can remove suspicious-looking growths before they can progress to cancer. Indeed, the new blood tests may paradoxically , according to a recent analysis by Ladabaum, if they drive people away from the traditional methods of detection.
In the meantime, other forms of prevention must also play a role. “With the main theory being that it’s linked to lifestyle choices and diet, that’s something that we can do something about,” says Bailey. Beyond the standard but useful prescription of eating less processed food, ditching sugary drinks and getting more exercise, other things have been found to be protective against CRC, including high consumption of , long-term use of and .
But perhaps most importantly, individuals, as well as doctors and medical professionals, must be made more aware of the risk of EOCRC, says Bailey. “There’s still a perception that young people are too young for colorectal cancer,” she says. As the millions of people under 50 facing a recent diagnosis will tell you, they are not.
Consult a doctor before making any changes to your medication.
Possible signs of colorectal cancer
Consult your doctor about:
▸ Diarrhoea or constipation that doesn't go away
▸ Changes in stool appearance, such as size or shape
▸ Rectal bleeding or blood in stool
▸ Abdominal pain or frequent cramping in the lower stomach
▸ Discomfort when sitting or during a bowel movement
▸ Sudden unexplained weight loss
▸ Anaemia
▸ Excessive fatigue
