What’s behind the worrying rise of cancer in YOUNG PEOPLE?

More people aged 18 to 49 are now developing the disease, and developed countries such as the UK are worst affected. We spoke to the scientists trying to work out what’s to blame...

CANCER has long been a disease that many people fear most — it is also a condition we associate with older age. But something alarming has been happening over the past three decades. While deaths from cancer continue to decline, younger people — including those who appear healthy and fit — are increasingly getting cancers that used to be the preserve of older age groups.

The diagnosis of the Princess of Wales at just 42 reflects a worrying, wider trend: for although early-onset cancers — defined as those that occur in adults between the age of 18 and 49 — account for only a fraction of the total cases, their incidence and death rates are growing significantly worldwide. and worst affected are countries in the developed world, including the UK.

early-onset cancer increased by 79 per cent between 1990 and 2019, according to analysis published in BMJ Oncology last year — with the number of deaths rising by nearly 28 per cent in the same period. The highest rates were in north america, Oceania (which includes australia, new Zealand and Hawaii) and western europe.

experts also say that for many with early-onset cancer, their prognosis tends to be worse, with lower, five-year survival rates. This could be down to molecular differences in early- onset tumours, which make them more likely to spread rapidly and resist treatment.

Meanwhile, survivors have a higher risk of long-term health problems such as infertility, heart disease and secondary cancers, according to the national Institutes of Health in the U.S.

There is little doubt the problem is rising. ‘Studies show the rates of early-onset cancers, particularly breast, colorectal, pancreatic, thyroid and cancers of the reproductive organs, have been consistently increasing over the past several years,’ says Dr Veda Giri, a leading expert in this field.

Younger patients face not just the long-term physical effects, says Dr Giri, who is director of the early-Onset cancer Programme and chief of the Division of clinical cancer Genetics at Yale School of Medicine in the U.S., there can also be psychosocial issues that impact patients’ quality of life.

‘There can be struggles with the impact on body image, mental health, substance misuse and social isolation,’ she says.

‘Many individuals with an earlyonset cancer diagnosis have childcare responsibilities, or have to juggle employment.’

In the UK, between the early 1990s and 2018, cancer incidence rates in 25 to 49- year- olds increased by 22 per cent. That’s a bigger percentage change than in any other age group, according to cancer research UK.

The most common early-onset cancer is breast, with more than 10,000 women under the age of 50 diagnosed every year (around a fifth of the total cases). The second most common is a category known as TBL: cancers of the trachea (windpipe), bronchus and lung.

colorectal cancer is another common early-onset cancer, with rates among adults aged 25-49 increasing by an alarming 48 per cent from 1993–2018, says Professor andrew Beggs, a consultant colorectal surgeon at Queen elizabeth Hospital, Birmingham.

‘early or young-onset cancer is far from rare. I run a clinic for early-onset cancer and we are seeing more and more people in their 40s with the disease,’ he says.

So why is early-onset cancer on the rise? Multiple studies have linked this to lifestyle factors, particularly diet and obesity — but there may be less obvious risk factors, such as changes in gut bacteria linked to antibiotic use.

Some of the most compelling evidence comes from a 2019 study by researchers at the University of edinburgh who, along with international epidemiologists, looked at the rates of 29 early-onset cancers in 204 regions. In their analysis, published in BMJ Oncology, they concluded that diets high in red meat and sodium (i.e. salt) and low in fruit and fibre, as well as alcohol intake and tobacco use, were the main risk factors.

They also identified obesity as a major risk factor, pointing out that it’s associated with chronic inflammation and oxidative stress (damage caused by molecules known as free radicals), which causes Dna damage which can lead to cancerous changes.

But that’s not the whole picture. Professor Karol Sikora, a leading consultant oncologist and the founding dean of Buckingham University Medical School, told Good Health: ‘although lifestyle factors play a major part, this can’t account for everything — lots of healthy younger people are getting cancer who don’t have obvious risk factors.’

The researchers in the 2023 study in BMJ Oncology suggested there was a link between pollution and the rise in the number of early-onset trachea, bronchus and lung (TBL) cancers. ‘Outdoor air pollution may be emerging as an important risk factor for early onset TBL cancer,’ they wrote.

could genes be to blame? In fact, cancers due to inherited

Disease more likely to spread in the young

Most common type is breast, then windpipe

faulty genes are much less common than those caused by other factors. Only around 10 per cent of early- onset colorectal cases have been associated with gene mutations, for instance, says Xavier Llor, a professor of medicine (digestive diseases) at Yale School of Medicine.

‘ While it’s true that genetic syndromes [for example, Lynch syndrome, which is linked to gastric and ovarian cancers] are more commonly the cause for younger patients than older ones, the numbers of these types of bowel cancer have remained quite stable over the years and can’t explain the sudden rise in cases we’ve seen,’ he says.

‘We have to conclude that the factors underlying rising earlyonset cancer are environmental or lifestyle related.’

Like Professor Sikora, he believes that while factors such as a sedentary lifestyle do play a role, ‘most cases remain unexplained’. ‘What we do know is that there is a “cohort effect”, meaning that all generations born after 1960 approximately have higher risks of colorectal cancer than individuals born before those dates.’

In other words, they share some, as yet unidentified, common behaviours and environmental factors they’ve been exposed to.

One possibility is changes in their gut microbiome, the community of fungi, bacteria and viruses that live in our gut and play an important role in inflammation and the immune system.

a study, published in the British Journal of cancer in January, identified certain types of harmful gut bacteria in colorectal tumours taken from 1,687 patients — the researchers found that earlyonset colorectal tumours (from patients under 45) had a different microbial profile than later-onset

types. ‘ a potential cause of this increasing incidence is related to changes in our gut microbiome,’ explained the lead researcher, daniel Buchanan, an associate professor who heads the Colorectal Oncogenomics lab at the University of Melbourne.

‘Over the past few decades our diet, lifestyle and environmental factors have changed, which can alter the type of bacteria — as well as the balance between good and bad bacteria that live in our gut.’

Studies have also linked the rise in cases to increased use of antibiotics. Research in the British Journal of Cancer in 2022, which looked at data from over 7,500 UK cases of colorectal cancer, found a link with antibiotic use in all age groups, but particularly in the early-onset cohort.

The researchers concluded that ‘antibiotic-induced microbiome changes can be permanent’ and affect the immune system’s ability to tackle rogue cells that turn into cancer. These changes may also allow ‘bad’ bacteria to flourish, ‘leading to inflammation and tumour formation’.

Dr Buchanan and his team identified three types of bacteria in the gut that produce chemicals that can damage dNa and lead to cancer. One strain in particular — a variant of e. coli that causes gastric infections — was more likely to occur in patients with early-onset colorectal cancer.

‘It’s the first time a non-genetic biomarker for the cause of colorectal cancer has been identified — we can now link the cause of cancer back to this bacteria,’ says dr Buchanan.

The researchers suggested that early exposure to this variant of e. coli, when our gut microbiome is still developing, may make someone more susceptible to developing early-onset tumours. social changes may also be driving the increase. More women are having children later in life, which appears to affect their child’s risk of developing childhood cancers (although whether that risk carries on until adulthood in unclear).

Compared with children born to mothers aged 20-24, those born to mothers in older age groups had a 13-36 per cent higher risk of paediatric cancer, reported the american Journal of epidemiology in 2017. The same study found that older fathers may also increase the risk.

Other researchers have suggested that the ‘environment’ in the womb of older mothers may affect which genes are switched on or off in their offspring, which makes them more likely to develop cancers later in life.

The rise may also have positive explanations, such as greater awareness. For example, the number of younger men being diagnosed with prostate cancer in the UK has doubled compared with 20 years ago.

But, as Christopher eden, a professor of urology at the Royal surrey County Hospital, Guildford, told Good Health: ‘Greater exposure of prostate cancer in the media is leading to greater detection. Men under 40 and with a family history are getting checked and this is one of the reasons that the average age at diagnosis has come down.’

Once diagnosed, patients with early-onset cancers face unique challenges. Fertility and family planning are much more likely to affect younger people with cancer, says Nancy Borstelmann, a clinical social worker and researcher into psychological and social issues around early-onset cancers, based at smilow Cancer Hospital in Connecticut.

‘some cancers and treatments can create challenges with being able to become pregnant or produce sperm.

‘depending on their age, some patients may face a decision about freezing eggs or embryos, or sperm banking,’ says dr Borstelmann. ‘Reproductive concerns can add to the distress that these patients are already experiencing, and are important for patients and their doctors to discuss.’

Could there be a link with types of gut bacteria?

WHY TREATMENT MAY DIFFER IF YOU’RE YOUNG

IF YOUNGER patients face issues specific to their age, they may also require an age-specific approach, as the same type of cancer can behave differently depending on age.

‘Studies have shown that when some tumours happen earlier in life, they actually have different molecular properties,’ says Professor sikora. ‘Cells within these early- onset tumours may mutate faster and be more aggressive, although no one is sure exactly why.’

A study that looked at genetic data collected from tissue samples from 1,757 cases of 14 earlyonset cancers (including breast, brain, uterine and colorectal cancers) found changes that suggested different genes were being switched on and off compared with later-onset cancers, reported

the journal Cell Reports in 2021. ‘Earlyonset cancers, like late-onset ones, are typically easier to treat the earlier they are diagnosed,’ says Professor Sikora. ‘However, early- onset cancers may respond better to targeted therapies such as immunotherapy because they mutate faster, and are more easily recognised by the immune system.’

Separately, some treatments can have long-term side-effects which may not be suitable for younger people raising families or with physical jobs, he explains. For example, oxaliplatin, a type of chemotherapy used to treat colorectal cancer, causes nerve damage in many, resulting in loss of sensation in the fingers, toes and, in more severe cases, the hands and feet.

With hormone-driven cancers, many early-onset cancers are already treated differently from the same cancers diagnosed later in life. ‘Take breast cancer, for example, which tends to be much easier to treat in women who are past the menopause,’ Professor Sikora told Good Health.

‘A woman diagnosed with breast cancer in her 80s is more likely to have slow- growing, oestrogen- positive

tumours which can be treated with tamoxifen, a drug that reduces the effect of oestrogen in her body.

‘A women diagnosed with breast cancer before the menopause is more likely to have triple-negative or HER2 breast cancers — which both require more aggressive treatments, especially if they have already spread.

‘Typically, a younger woman with any type of invasive breast cancer will need surgery, followed by radiotherapy and chemotherapy, with tamoxifen taken for five years to stop it coming back,’ he adds.

Meanwhile, the nature of prostate cancer may also be different in younger men. ‘It may be more aggressive than in old age, leading to significant complications and death rates — and have different causes than later-onset disease,’ says Professor Eden.

The younger a man is when diagnosed, the lower his chances of surviving five years. ‘ This is partly because it is not being caught early enough, as doctors and patients don’t expect to see these cancers early in life,’ says Professor Eden.

While a faulty BRCA2 gene may raise a man’s risk of early- onset prostate cancer, it only accounts for around 2

per cent of cases under the age of 50. ‘So there are clearly other contributing factors that we don’t yet know,’ says Professor Eden.

There is some good news. Earlyonset cancers respond just as well to chemotherapy, according to Andrew Beggs and ‘young, fit people cope better with chemotherapy and can have higher doses without permanent damage to themselves. If higher doses of chemotherapy can be tolerated the tumour may respond better’, he says.

Dr Claire Knight, a senior health information manager at Cancer Research UK, told Good Health that the risks of early-onset cancers had to be kept in proportion.

‘However alarming this might seem, cancer is primarily a disease of older age,’ she says. ‘If people are concerned about their cancer risk, there are ways to reduce it, such as not smoking, having a balanced diet, getting plenty of exercise and staying safe in the sun.’

Dr Llor concurs: ‘Decreasing your body weight, even a small amount, can make a big difference in terms of cancer risk.’ As does the type of food we eat. ‘Less red meat, more vegetables, and fruits. All of those things do have a very important impact,’ he says.