Increase in CRC in Under 50s Confirmed Across Many Countries

Liam Davenport

May 28, 2019

The significant increase in the incidence of colorectal cancer (CRC) in people younger than 50 years, already reported in the United States, has also been seen in many countries across Europe, as well as Australia, New Zealand, and Canada.  

Three new studies report the same finding of a significant increase in incidence, and the authors say it cannot be attributed to earlier detection.

The increase in CRC in the under 50s in the US has already been noted over the last 2 years, and experts have told Medscape Medical News that this is "an issue screaming for attention."

However, "not everyone buys into the fact that these increases are real," commented Reinier G.S. Meester, PhD, Stanford University School of Medicine, Redwood City, California, "so that's a reason why we did this study."

Meester and colleagues looked at incidence patterns in almost 30,000 patients with CRC aged 40-49 years diagnosed over a 40-year period in nine US regions.

The findings, published as a research letter in the May 21 issue of JAMA, revealed that, between 1995 and 2015, there were significant increases in CRC cases in this age group, with the greatest increase seen in distant disease, at an increase of 2.9% per year.

This was underlined by a significant rise in the proportion of distant disease cases, from 22% in 1995 to 27% in 2015, that could not be explained by the decrease in the number of unstaged cases over the same period.

This suggests that "there has been a real increase in risk and that the trends do not represent a shift in age at diagnosis attributable to earlier detection," they conclude.

Increase Also Seen in Europe, Australia, and Canada

The second study, published online on May 16 in The Lancet Gastroenterology & Hepatology, looked at trends in the incidence of CRC in cancer registries in Australia, Canada, Denmark, Norway, New Zealand, Ireland, and the UK.

The authors, led by Marzieh Araghi, PhD, International Agency for Research on Cancer, Lyon, France, found that, while overall cancer rates decreased or stabilized, there were significant increases in rates of both colon and rectal cancer in several countries among people younger than aged 50 years.

The increase was around 3% per year in Denmark, New Zealand, and Australia for colon cancer, and that for rectal cancer was 3.4% in Canada and 2.6% in Australia.

Highest Increase in Adults Aged 20-29 

In the third study, Manon C. W. Spaander, MD, PhD, Erasmus MC University Medical Center, Rotterdam, The Netherlands, gathered data on over 140 million individuals aged 20-49 years in 20 European countries.

The research, published online May 16 in Gut, showed that the increase in CRC incidence was highest in those aged 20-29 years, at almost 8%, followed by nearly 5% in those aged 30-39 years, and just over 1.5% in 40-49 year olds.

"Until the underlying cause of this trend is clarified, it would be commendable to raise clinicians' awareness and identify factors possibly associated with this trend," the team comment.

Should the trend in CRC incidence continue, "screening guidelines may need to be reconsidered," they add.

Lower Age to Start Screening?

Lowering the age at which to start screening has already been the reaction of some groups. In 2018, the American Cancer Society recommended CRC screening should start at 45 years of age in the United States.

The usual age to start is 60 years in most countries that do CRC screening.

However, Araghi commented in a press release that population-based CRC screening in the under 50s may not be cost-effective because of the relatively low incidence of the disease. Although the incidence of CRC has increased, the absolute risk is low.

Araghi added that instead of screening everyone, the lower screening age could be targeted to those at greater risk. For example, "family history could help to identify younger people at high-risk of genetic susceptibility to colorectal cancer for further assessment."

"However, future studies are needed to establish the root causes of this rising incidence to enable the development of effective preventive and early detection strategies," she added.

What's the Cause of the Increase?

Looking at the three studies as a whole, Meester told Medscape Medical News that the cause of this trend of increased CRC incidence among younger adults remains "a mystery" at this stage.

It has been suggested that obesity and processed foods are likely factors, but their role is "still to be much better understood," he commented.

Smoking is also a known risk factor for CRC "but that has been decreasing in most populations," he added.

Meester said that more studies of the genetics, and epigenetics, underlying the early onset of cancers are therefore needed "to get a better understanding of what may be driving this."

He believes that the new studies "make a stronger case for screening earlier."

He argues that lowering the screening age has even been shown to be cost-effective, although he noted that this may be "setting specific."

"In the United States, treatment costs are extremely high, so it's easier to get cost-effective prevention strategies for cancer," he said, adding that this "may not be generalizable" to countries such as the UK.

In a commentary accompanying the study by Araghi et al, Giulia M. Cavestro, MD, PhD, Raffaella A. Zuppardo, MD, and Alessandro Mannucci, from Vita-Salute San Raffaele University, Milan, Italy, agree with the need to lower the CRC screening age.

However, they emphasize that "other initiatives" are also required.

"Public awareness campaigns are essential to increase adherence to screening, and more gastroenterology units are likely to be needed," they comment.

In addition, "the lower age for screening should not be one-size-fits-all — personal and family history should be taken into account," they add.

Need for Urgent Investigation

Several UK experts have commented on the articles reporting an increase in CRC incidence published in The Lancet Gastroenterology & Hepatology and Gut.

"Both publications show a clear increase in recent incidence of colorectal cancer in people under age 50 in several developed countries," commented Stephen Duffy, MSc, professor of cancer screening at Queen Mary University of London, UK.

"Both papers suggest that sedentary lifestyles, being overweight, and dietary factors may be partly responsible for this. This is almost certainly the case, but it is probably not the whole story," commented Duffy.

"In terms of screening or prevention, it is probably too early to change policy since, despite the recent increases, the incidence in people under age 50 remains very low in absolute terms," he said.

"What is reassuring is that, while incidence is rising, mortality from the disease is falling, probably due to a combination of earlier diagnosis and improved treatment," he added.

Andrew Beggs, MBBS, PhD, consultant colorectal surgeon and Cancer Research UK advanced clinician scientist at the University of Birmingham, UK, added that the reasons underlying the increased CRC incidence "aren't clear" but "must be urgently investigated."

He noted that both studies were of "high quality...and so we can be confident from this that the conclusions the authors have reached are correct."

He supports the idea for lowering the age at which to start CRC screening, but he also emphasizes that anyone with any 'red flag' symptoms needs "to get it checked out as soon as possible." These include bleeding, a change in bowel habits, weight loss, or abdominal pain.

Marco Gerlinger, MD, team leader in translational oncogenomics, Institute of Cancer Research, London, UK, noted that the studies provide "solid data" to support trends that have been noticed "for some time now."

As well as indicating the need for more research, he believes "these results are a call to action to raise awareness among staff in family practices and hospitals to consider bowel cancer as a diagnosis when young people come to them with pain, changes in bowel habits, or blood in their stool."

Meester's study was supported by a fellowship from the Netherlands Organisation for Scientific Research and a grant from the National Cancer Institute, National Institutes of Health. Araghi's study was funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, Cancer Society of New Zealand, NHS England, Norwegian Cancer Society, Public Health Agency Northern Ireland, Scottish Government, Western Australia Department of Health, and Wales Cancer Network. Disclosures for the other authors are listed in the articles.

JAMA. 2019;321:1933-1934. Research letter

Lancet Gastroenterol Hepatol. Published online May 16, 2019. Abstract

Gut. Published online May 16, 2019. Abstract

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