Significant increase in early-onset colorectal cancers in the UK and Ireland, meeting hears

Irish Society of Gastroenterology Winter Meeting, in conjunction with the Irish Association of Coloproctology, 12-13 November 2020

Doctors are seeing colorectal cancer in a ‘surprisingly’ young patient cohort, the President of the Irish Society of Gastroenterology (ISG) told the society’s Winter Meeting, which was held in conjunction with the Irish Association of Coloproctology and took place virtually on 12-13 November.

Dr Tony Tham was speaking in advance of a talk by Prof Matt Rutter of North Tees and Hartlepool NHS Trust, who was discussing ‘The rise of early onset colorectal cancer’.

Welcoming Prof Rutter, who is the Clinical Director of the Trust’s bowel cancer screening programme, Dr Tham said the topic was of great concern “because a lot of us are seeing colorectal cancer presenting in a surprisingly younger age group”.

Beginning his talk, Prof Rutter said that doctors would be all too familiar with headlines about colorectal cancer deaths, which seem to be increasingly frequent. His talk examined why the disease might be increasing and then discussed possible management strategies to deal with the issue.

Defining early-onset colorectal cancer (EOCRC) as cancer detected before the age of 50, he said: “We all know that cancer and particularly bowel cancer is an age-related disease. Globally there is just shy of two million new diagnoses every year.”

90 per cent of these will be diagnosed in people above the age of 50, with 31 per cent diagnosed in those aged 75 years or older.

“This does mean that 10 per cent will be diagnosed in people aged less than 50 years,” Prof Rutter said.

In terms of late-onset colorectal cancer, its incidence and mortality have decreased since the early 1990s, with the extent and time of the decrease varying from nation to nation. This reduction has many contributing factors, the meeting heard, including screening, the reduction in risk factors such as smoking, and perhaps the increased use of drugs such as aspirin. Improvements in treatment have also played a part.

Conversely, while the incidence of late-onset colorectal cancer has reduced over time, in EOCRC there has been an increase. It has been calculated in the US that despite the ageing population, by 2030 11 per cent of colon cancers and 23 per cent of rectal cancers will be EOCRC.

“A publication in Gut in 2019 gives us a more global picture,” according to Prof Rutter.

“Korea tops the chart. Two of the three countries that show a reduction in EROC are Italy and Austria. But broadly speaking it is the Western nations that have seen an increase in EOCRC.

“There has been a significant increase in early-onset colorectal cancers in the UK and Ireland. These are two of the nations with the highest increase.”
He said that research has found that the greatest increase can be seen in 20-29-year-olds, with the greatest increase in colon cancer.

“However, late-onset colorectal cancer is still the most common and we do need to bear that in mind.”

In terms of absolute risks, both sexes are equally affected. In US data, EOCRC is more common in ethnic minorities and, when it does occur, these patients are more often presenting at a later stage, symptomatic and poorly differentiated.

“But EOCRC has a better stage-adjusted disease-specific survival, compared to late-onset colorectal cancer,” he added.

Causes

Focusing on genetic disposition, Prof Rutter said it was known that this is higher in younger people. In those who received their diagnosis at a very young age, approximately a quarter of them will have Lynch syndrome.

“Contrast that with late-onset colorectal cancer where only about 3 per cent have Lynch Syndrome. Genes undoubtedly play a role in some patients that have EOCRC, but even with very young people, two-thirds of them will have no genetic predisposition and no family history.”

The gene pool is relatively stable over time, the Professor said, and most EOCRCs do not have pathogenic gene variants of family history.

“Although genes may play a role in some patients, they certainly do not explain this increase in recent generations for EOCRC.”

Plotting cancer incidence by date of birth had shown there is a clear ‘birth cohort effect’. This suggested that changes occurring early in someone’s life, such as environmental factors or lifestyle factors, such as diet, may well account for the current increase, said Prof Rutter.

Turning to diet and obesity, there was a clear association between obesity and weight gain and colorectal cancer risk, although only 10 per cent of all cancers can be attributed to adult obesity.

“With EOCRC, the evidence is more limited, but we are already seeing some associations, including with high birth weight, high BMI during childhood and puberty, and weight gain during young adulthood.”

He again pointed to the example of Korea, which went from experiencing food shortages to the large scale adoption of fast food and the Western diet, following the dramatic economic growth after the end of the Korean War.

“Korea has seen one of the largest increases globally in BMI in both adults and children,” he said.

Turning to the US, he said there was a clear correlation between the incidence of EOCRC and the prevalence of self-reported adult obesity.

“There are however some inconsistencies. We see similar increases in BMI in Germany, Austria, and Italy. And yet it is only in Germany that we have seen an increase in EOCRC.”

There has been a dramatic change in global food supply over the decades, he said. It might be specific new food components or an overall access in nutrients, which is causing this increase in cancer at a young age.

“There is evidence that access nutrients, particularly from processed foods or high glycaemic load carbohydrates, may initiate chronic low-grade inflammatory responses in metabolic cells. This so-called inflammatory diet is conducive to colonic proliferation, and maybe it is this that’s increasing the colorectal cancer risk.”

Studies have shown that even with moderate consumption of sugar-sweetened drinks, there is an increase in colorectal cancer, and Prof Rutter highlighted an animal study, which showed that there is a significant increase in cancer in animals fed high fructose corn syrup diets.

While he said there was a range of suggested potential risk factors, he particularly wanted to point out the possibility that our microbiome has changed.

“There are a number of potential reasons for this. It may come down to the changes in diet that I have mentioned, but we also know that there have been significant changes in the use of antibiotics over time. There is a reduction in the use of vaginal delivery and in breastfeeding, both of which we know can change the microbiome.

This is certainly a plausible and quite attractive explanation for why we may be seeing this increase. Clearly, we would need more research.”

He said that education and awareness of EOCRC should be increased in both clinicians and the public.

“We need to be alert to the possibility that a young patient presenting with symptoms may be presenting with cancer.”

Policymakers should also be educated as research into this area should be prioritised, he said.

“Clearly we need to do a lot more work understanding the aetiology of this increase. We need to know where those early onset risk factors differ from the more established risk factors that we know for more late-onset colorectal cancer. We really need to start research from scratch.”

Risk factors need to be examined from a person’s birth onwards, he continued.

“Once those have been established, we can start to understand the underlying mechanisms for early-onset colorectal cancer.

“Then we can start to do something about it.”

He was concerned about the birth cohort effect, saying “the key question is what will happen to those people when they start to age?”.

“The real concern is are we going to start to see a resurgence of increased incidence of late-onset colorectal cancer?”

Lifestyle modifications were needed “but these needed to be driven by better, quality evidence”.

“Adjusting screening programmes should also be considered”, he said.
“We can do this in one of two ways. We can reduce the starting age screening for everybody or we can start to move towards a more risk-stratified, personalised screening programme. Most countries will start their bowel cancer screening programmes between the ages of 50 and 60. That’s true of the UK and Ireland”

Two of the exceptions are Italy and Austria, he went on to say, both of which start screening in the patient’s fourth decade.

“They have been doing this for many years and these are two of the nations that have seen a reduction in early-onset colorectal cancer. More interestingly that reduction has been confined to those people who are of a screening age, 40 to 49-year-olds. All of this is compelling evidence to suggest that screening may impact on early-onset colorectal cancer as well as late-onset colorectal cancer.”

In 2018, the American Cancer Society lowered the screening age to 45. This was because they had demonstrated that a 45-year-old had the same risk as a 50-year-old had in 1993.

This also made sense from a health economics point of view. However, it was important to bear in mind that the majority of cases of cancers will still occur in older people.

Concluding his talk, the professor said that work was being carried out looking at models for risk, such as genetics and lifestyle risk.

“I think we are going to see more and more work in this area, particularly as we start to crunch big data with artificial intelligence.”

In summary, there was clear evidence that there is a concerning increase in EOCRC, the meeting was told. However, the absolute incidence was not so much of an issue at present, as cancer remains an age-related disease.

“But young people have the potential to lose more life years, and on a health economic argument we should be considering changing the screening age range to address this issue,” he said.

“In my eyes, the bigger concern is why this is happening.”

He said that the two most plausible explanations relate to diet or to changes in the microbiome.

“And of course those two may well be interrelated,” he said. “We need more research in this area. We need proper high-quality population-wide research.”

His biggest concern is that as the most recent birth cohorts age, a resurgence of late-onset CRC may be seen. “Although screening may help to mitigate this risk, we do need to bear in mind that those with potential lifestyle risk factors are exactly the people less likely to participate in screening. So screening may not be the whole answer here.”

The meeting’s Co-Chair, Dr Garret Cullen from St Vincent’s University Hospital, Dublin, described the presentation as a “fantastic” talk.
“I think it’s something we have all seen in clinical practice,” he said.

Responding to questions from the audience regarding fecal immunochemical tests (FIT) , Prof Rutter said it is a very effective test.

“It is much better at delineating someone’s cancer risk, than the patient’s symptoms. I think there is a real opportunity here to try to capture patients at a young age by using the FIT test as an easy early option to stratify a patient’s risk.”

He added that the younger a patient is the less likely that a FIT positive test will signify cancer.