Cancer mystery as cases rise among younger people around the world

When it comes to cancer research, we regularly hear good news about the number of people benefiting from advances in treatment. But there is one bad news story about the condition that gets little attention. For three decades, there has been a gradual rise in the number of people under 50 being diagnosed with cancer – and we don’t entirely know why.

The rise is steepest in bowel cancer, but an increase in incidences is happening with tumours of nearly all the major organs of the body. It is so alarming that it was made a top priority for research in a joint UK-US cancer funding review earlier this month. So, what might the causes be?

The incidence of cancer rises with age, mainly because the cells of older people have had longer to acquire the genetic mutations that cause tumours.

Around 9 in 10 cancerous tumours occur in people over 50, so the increasing incidence in people younger than this isn’t making a big impact on the total number of cases. “It’s important to remember that the vast majority of cancer cases are diagnosed in people over 50,” says Alice Davies at Cancer Research UK (CRUK).

Yet the trend is worrying, partly because it shows no signs of stopping. Young people should be in the prime of their lives and are often caring for children, says Marios Giannakis at the Dana-Farber Cancer Institute in Boston, Massachusetts.

“It’s an absolutely devastating day when you see young patients diagnosed with cancer,” he says. Giannakis called for an investigation into the reasons behind the rise in bowel cancer specifically in an opinion article in the journal Science on 16 March.

For most types of tumour, their increase in people under 50 has been relatively modest so far. For instance, the incidence of all cancers combined among 25 to 49-year-olds in the UK rose by 22 per cent between 1993 and 2018, from 133 cases per 100,000 people to 162 per 100,000.

But the fact that the same trend is being seen in many different cancer types in high, middle and low-income countries suggests that it should be seen as an emerging global epidemic, said Shuji Ogino at Harvard Medical School in a review of World Health Organization figures last year. “I believe the trend won’t stop anytime soon and it may accelerate,” he says.

The figures for bowel cancer are the most alarming, with about a 50 per cent rise in people aged 25 to 49 since the 1990s in the UK, for example. There is a similar pattern in the US, Canada, Australia, South Korea and several European countries, including Sweden, Finland and the Netherlands.

At first glance, the phenomenon might be ascribed to the relatively recent practice of cancer screenings finding tumours that wouldn’t otherwise have been noticed, but this could only be causing some of the increase. In the majority of countries, screening is only offered to people from about the age of 50, depending on the tumour type. Most of the cancers that are rising also can’t be screened for.

In addition, the rise in bowel cancer seems steepest among those in the youngest age bands, who are rarely offered screening. Across 20 European countries, the rise has been by about 2 per cent per year in people in their 40s, 5 per cent in those in their 30s and 8 per cent in those in their 20s.

This suggests that whatever the cause is, it is intensifying, says Manon Spaander at Erasmus University Medical Center in Rotterdam, the Netherlands, who helped to demonstrate this decade-based pattern in a 2019 analysis.

Another cause for concern is that some of the cancers that are rising in people under 50 seem to be more aggressive than those in older people. This is the case for tumours of the bowel, breast and prostate. That may be partly because younger people take longer to be diagnosed, perhaps because cancer is less likely to be suspected in this age group. Tumours in people under 50 are also more likely to have certain innate features, such as genetic mutations that are harder to treat.

In most cases, cancers are thought to take several decades to develop, as cells gradually acquire more and more mutations that let them escape our bodies’ natural brakes on cell replication. If people are developing tumours in their 20s, 30s and 40s, it is probably because of things they have been exposed to in their childhood or perhaps even while in the uterus, says Ogino.

The most obvious suspicion is that this increase in cases is something to with changes to our diet, especially because the largest rise is in bowel tumours, with our digestive system coming into direct contact with the food we eat. In fact, of the 14 cancer types where a rise has been recorded in under-50s, eight involve some part of the digestive system, such as the oesophagus (or food pipe), stomach and gall bladder.

It was already thought that some aspects of the Western diet, such as eating a lot of red or processed meat, could raise the risk of bowel cancer. Supporting this, the biggest rise in bowel cancers in those aged 18 to 49 – classed as early onset – has been in tumours that arise in the lower portion of the bowel and rectum, next to the anus, and these cancer types are those most often linked with eating processed red meat, says Giannakis.

But the claims for the cancer-causing properties of red meat are contested and there are many other features of Western-style diets that could be responsible, including sugar, fat, ultra-processed food and refined carbohydrates such as white bread, as well as a lack of fibre. Another suspect is what is arguably one of the Western diet’s net effects: a rise in obesity levels. Some studies suggest that people who are overweight or obese have a higher rate of certain cancers.

The cause may not even be directly related to what food people eat, but some other aspect of modern life, including the shift to a more sedentary lifestyle or our increasing exposure to certain environmental pollutants.

Another possible cause is the use of antibiotics because of their potential impact on our gut bacteria. The timing fits, as antibiotics came into use in the 1950s and people who were then children would have reached their 40s in the 1990s, when the rise in early-onset cancer began, says Spaander.

With so many possible causes, finding out the answer has to be a priority for cancer research, two major funders – CRUK and the US National Cancer Institute – have agreed. Earlier this month, the organisations made this goal one of their nine joint research priorities, which they call Cancer Grand Challenges.

We need huge long-term studies that follow people from a young age and record their eventual rates of cancer, tracking their lifestyle and environments – sometimes called their exposome – while taking regular samples of blood and, ideally, faeces, says Sherene Loi at the University of Melbourne, Australia, who helped to set up the Cancer Grand Challenges.

Fortunately, this Herculean research doesn’t need to be started from scratch as there are many such studies that have already been set up to investigate the relationship between our health and lifestyle. Cancer researchers could piggyback their efforts onto these to extract the relevant data, she says.

For now, it would be premature to advise the public to avoid any of the mooted risk factors before we have answers, says Loi. “We don’t yet understand any of the reasons,” she says. “At the moment, we’re just poking around in the dark.”