The increased incidence of colorectal cancer (CRC) in younger adults is not simply a demographic shift but reflects potential biological changes in the disease as well as alterations in geographical distribution that need to be better understood, say UK researchers in a large population-based study.

Numerous recent studies from the US, as well as those in countries across Europe, Australia, New Zealand, and Canada, have shown that there has been an increase in CRC incidence in younger people in the past few decades.

As reported by Medscape Medical News, these studies suggest that, while the overall incidence of CRC may have stabilised, the incidence in adults aged under 50 years has risen sharply, at rates ranging from 1.5% to 8% per year.

Seeking to provide a more detailed picture of the shift, Adam Chambers, School of Cellular and Molecular Medicine, University of Bristol, and colleagues looked at data on more than 56,000 UK adults aged 2049 years diagnosed with the disease between 1974 and 2015.

The new research, published online by the British Journal of Surgery, showed that, following an initial dip in incidence, rates increased initially in adults aged 2029 years, followed by those aged 3039 years, at rates of up to 6% per year.

While gender and socioeconomic status did not appear to have an impact on the change in incidence rates, there were notable geographic variations, with the largest increases in southern England, and distal tumours were found to be the biggest driver of new cases.

Mr Chambers commented in a news release: "Age has always been a major risk factor for bowel cancer, with the majority of cases being diagnosed in patients over 60 and therefore bowel cancer screening has focused on older age groups.

"However, this study shows that over the past 30 years, there has been an exponential increase in the incidence of bowel cancer among adults under 50."

Co-author David Messenger, a consultant colorectal surgeon at Bristol Royal Infirmary, added: "Future research needs to focus on understanding why this trend is occurring and how it might be reversed, potentially through the development of cost-effective testing strategies that detect tumours at an earlier stage or polyps before they become cancerous."

Mr Messenger told Medscape News UK that, while this is a population-based study and cannot demonstrate cause and effect, he believes that there are likely to be multiple factors underlying the trend that are "not necessarily the same" for different countries or regions.

He believes that "undoubtedly some of it is dietary related and some of it also obesity related" but, unlike in, say, lung cancer, it is "much more difficult to pick apart" the relationship between lifestyle factors and the development of CRC.

He said that, "based on when weve seen the rise in incidence, it is probably something to do with how our lifestyles have changed really from the mid-60s onwards" because, for successive generations from that period, "youve got a cohort effect" of increasing incidence.

Mr Messenger also notes that the shift in tumour location and the shift in geographical distribution of cases suggests that "the biology of the disease in young adults is different", which could have healthcare implications if the increase in CRC incidence in younger patients continues.

The authors point out that, while increases in rates of CRC have been observed in younger adults across Europe and North America, there appear to be differences in the way the disease manifests in younger versus older populations.

They note that it therefore is "vital" that the epidemiology underlying the increase is better understood, "as young adults typically present with more advanced tumours that carry a poorer prognosis".

To investigate further, the team examined data from the UK-wide National Cancer Registration and Analysis Service database on all adults aged 2049 years diagnosed with CRC between 1974 and 2015.

They also obtained population estimates from the Office for National Statistics and the European Standard Population report to examine trends in age-specific incidence rates, stratified by sex, anatomic subsite, Index of Multiple Deprivation quintile, and geographical region.

The researchers identified a total of 1,145,639 new cases of CRC diagnosed during the study period, of which 2594 were in adults aged 2029 years, 11,406 among 3039 year olds, and 42,314 in those aged 4049 years.

Joinpoint regression analysis revealed that after an initial decrease, there was a notable increase in cases among individuals aged 2029 years, at an annual percentage change (APC) of 4.6% in women from 1986 and 5.1% in men from 1992.

In adults aged 3039 years, the increase started later, at an APC in women of 3.8% from 1995 and 6.0% in men from 2002.

The increases were smaller in adults aged 4049 years and started later, at an APC of 1.5% in women and 0.8% in men, beginning in 2003.

These results, the team writes, are "suggestive of an age cohort effect".

Looking at the data in more detail, they found that the incidence of proximal CRCs, primarily driven by caecal and ascending colon cancers, was increased in 2029 year olds, at an APC of 4.4% from 1995, and in 3039 year olds, at an APC of 5.8% from 2005, but not in 4049 year olds.

However, the increase in incidence rates for distal cancers was higher and more sustained, at an APC of 5.6% from 1991 for 2029 year olds, and an APC of 3.3% from 1995 to 2006 and 7.0% from 2006 for adults aged 3039 years. For those aged 4049 years, the APC was 1.4% from 2001.

While there were few differences noted when stratifying individuals by socioeconomic status, there were differences observed when the researchers looked at geographical region.

For example, incidence rates of proximal CRC among 2049 year olds were, in 1985, decreasing all across England apart from in London, with the South West recording an APC of -12.1%.

By 2015, however, incidence rates for proximal CRC were increasing fastest in the South East at an APC of 7.4%, in London by 6.5% per annum, and in the East at an APC of 6.0%.

The increase was even greater for distal cancers, with all southern regions showing annual increases in incidence rates of more than 5%, rising to an APC of 10.1% in the South West.

"It is difficult to explain why incidence rates are increasing more rapidly in young adults in the south given that risk factors such as obesity are increasing faster in northern regions," the team says.

While acknowledging there may be issues around access to healthcare at play, they add: "The role of environmental factors, such as diet, obesity, physical exercise and the gut microbiota, in the development of youngonset colorectal cancer is incompletely understood and requires further research."

Mr Messenger said the evidence nevertheless suggests that the biology of CRC in younger adults differs from that in their older counterparts.

"That then begs the question about what is happening in the UK that were seeing such pronounced increases in southern regions," particularly in terms of the dramatic increase in CRC cases in the distal large bowel.

He highlighted that, "typically, people have thought this is maybe a disease that is perhaps related to lower socioeconomic groups but weve not seen that in our study the increased rates have occurred equally across all socioeconomic groups in the younger adult age group".

However, Mr Messenger noted that, over time, there has been northsouth migration in England, as well as "increasing urbanisation in southern regions, particularly the South West".

He pointed to cities such as Bristol and towns along the M4 corridor, including Swindon, which are increasing in size and becoming more and more urbanised. In contrast, Middlesborough and Teeside are depopulating, a phenomenon he ascribes to internal migration.

Mr Messenger added that, as well as tumours in younger adults having a "greater propensity to be in the sigmoid and the rectum, theres some evidence that molecularly, they are slightly different; they dont necessarily exhibit microsatellite instability in the same way that you see with older adults".

He said that this observation cannot currently be fully explained, and is the focus of future research. There is also evidence to suggest that younger adults are more likely to present with metastatic or locally advanced disease.

He believes that screening could therefore help with identifying patients at an earlier stage, although not via the blanket use of flexible sigmoidoscopies or colonoscopies but rather greater application of faecal immunochemical testing, which is currently being used in the over-50s.

"The question is do we then roll that out to adults under 50 as a means of risk stratifying those groups, as to whether or not they should have endoscopic examination," Mr Messenger asked.

This would also be a way of obtaining more data on whether young adults really do present with more advanced disease.

"Weve got some idea that they might do worse because theyve got more advanced disease but that is really not set in stone and there is virtually no data on that in the UK, so thats really where things will be heading," he said.

If the current trends continue unchecked, Mr Messenger believes that the types of cases "that we see in 20 years time will look very different".

"At the moment, we think that about 5% of all bowel cancer occurs in adults under 50 but if you were to extrapolate out those rates of increase out to 2041we think it could account for anywhere from about 8% up to 30% of all cases, so youve got the potential in 20 years that patients with bowel cancer could be a very different group."

He continued: "This is anecdotal but Im seeing a lot more younger adults with advanced disease.

"So overall, globally in the population, probably the incidence will trickle down and everyone will think thats great, but actually if you look at it more deeply, those that are getting the cancers will be different. It will be younger adults with more advanced disease."

Mr Messenger said: "Suddenly were having a paradigm shift from where this is seen as a disease of middle age and elderly to then becoming a disease of a younger population."

The study was funded by the Medical Research Council, David Telling Charitable Trust and the Elizabeth Blackwell Institute.

No conflicts of interest declared.

Br J Surg 2020. doi 10.1002/bjs.11486

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Increase in Younger Bowel Cancer Cases Highest in Southern England - Medscape