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Young-onset colorectal cancer

Abstract

In the past decades the incidence of colorectal cancer (CRC) in people under the age of 50 years has increased, which is referred to as early-onset CRC or young-onset CRC (YO-CRC). YO-CRC is expected to account for 11% of colon cancers and 23% of rectal cancers by 2030. This trend is observed in different parts of the world and in both men and women. In 20% of patients with YO-CRC, a hereditary cancer syndrome is found as the underlying cause; however, in the majority of patients no genetic predisposition is present. Beginning in the 1950s, major changes in lifestyle such as antibiotic use, low physical activity and obesity have affected the gut microbiome and may be an important factor in YO-CRC development. Owing to a lack of screening, patients with YO-CRC are often diagnosed with advanced-stage disease. Long-term treatment-related complications should be taken into account in these younger patients, making the more traditional sequential approaches of drug therapy not always the most appropriate option. To better understand the underlying mechanism and define relationships between environmental factors and YO-CRC development, long-term prospective studies are needed with lifestyle data collected from childhood.

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Fig. 1: Global incidence of YO-CRC.
Fig. 2: Pathogenetic mechanisms in hereditary YO-CRC.
Fig. 3: Pathogenetic mechanism of sporadic YO-CRC.
Fig. 4: Endoscopic imaging and histology of the tumour in a patients with YO-CRC.
Fig. 5: Proposed algorithm for the management of YO-CRC.

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Acknowledgements

The authors thank A. Hahn for her contribution to the article.

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Authors and Affiliations

Authors

Contributions

Introduction (M.C.W.S.); Epidemiology (A.G.Z.); Mechanisms/pathophysiology (M.C.W.S. and S.S.); Diagnosis, screening and prevention (M.C.W.S., M.J.B. and E.J.K.); Management (J.J.S. and Y.N.Y); Quality of life (Y.N.Y.); Outlook (M.C.W.S.); Overview of Primer (M.C.W.S.).

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Correspondence to Manon C. W. Spaander.

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Nature Reviews Disease Primers thanks N. Hoogerbrugge, M. G. Dunlop and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Age–period–cohort modelling

An analysis that examines three distinct time occurrences: age, period and cohort effects. The analysis seeks to estimate the independent effects of these three phenomena with respect to the outcome of interest for the study.

Birth cohort effect

The effect that having been born in a certain time or period, or having experienced the same life experiences, has on the development or perceptions of a particular group.

Familial adenomatous polyposis

(FAP). A hereditary disorder characterized by the presence of hundreds to thousands of (precancerous) colorectal adenomatous polyps caused by mutations of the tumour suppressor gene encoding adenomatous polyposis coli.

Joinpoint analysis

A regression analysis that fits a series of joined straight lines on a log scale with respect to trends in the cancer incidence and mortality rates, adjusted for age. Line segments are joined at points called joinpoints.

Low anterior resection syndrome

A constellation of symptoms that may develop after a low anterior resection including faecal incontinence, urgency or feelings of incomplete emptying.

Lynch syndrome

A hereditary disorder associated with an increased risk of many types of cancer, particularly colorectal cancers caused by mutations in the DNA mismatch repair genes (MLHL, MSH2, MSH6, PMS2 and EPCAM).

Markov model analysis

An analysis to forecast the value of a variable, which assumes that future states depend only on the current state and not on events that have occurred before it or prior activity.

Penetrance

The proportion of people with a particular genetic variant (or mutation) who exhibit signs and symptoms of a genetic disorder.

Polyposis

The formation of a substantially greater number of colorectal polyps than in the general population.

Serrated pathway

A pathway that describes the progression of sessile serrated adenomas and traditional serrated adenomas to colorectal cancer.

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Spaander, M.C.W., Zauber, A.G., Syngal, S. et al. Young-onset colorectal cancer. Nat Rev Dis Primers 9, 21 (2023). https://doi.org/10.1038/s41572-023-00432-7

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