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.

Figure 1.. Global incidence of YO-CRC.

Age-standardized incidence of young-onset colorectal cancer (YO-CRC; age 20–49 years) in both sexes worldwide for the year 2020. Countries/regions with the greatest percentage increase for years 2008–2012 are depicted in red.[8]

Figure 2.. Pathogenetic mechanisms of hereditary YO-CRC.

The schematic depicts the cellular phenotype and intracellular events in hereditary colorectal cancer (CRC) development. Hereditary CRC syndromes are caused by pathogenic variants in many different genes, which affect different molecular pathways in each hereditary syndrome. APC, adenomatous polyposis coli; FAP, familial adenomatous polyposis; IHC, immunohistochemistry; MAP, MUTYH-associated polyposis; MMR, mismatch repair; MSI, microsatellite instability; MSS,: microsatellite stability PPAP, polymerase proofreading-associated polyposis; SPS, serrated polyposis syndrome.

Figure 3.. Pathogenetic mechanism of sporadic YO-CRC.

Examples of risk factors, during the life-course that may be involved in the development of young-onset colorectal cancer (YO-CRC), including environmental exposures, medication use and diet. All these factors influence the gut microbiota, creating a susceptible environment for CRC by inducing inflammation, suppressing immunity and promoting tumour growth.

Figure 4.. Endoscopic imaging and histology of a YO-CRC case.

a, b| Endoscopic imaging of a tumour in the sigmoid colon of a 45- year old woman diagnosed with sporadic young-onset colon cancer (YO-CRC). c, d| Histology of a surgically resected tumour specimen from the same patient.

Figure 5.. Proposed algorithm for the management of YO-CRC.

Treatment follows the same principles as for later-onset colorectal cancer (CRC) and the approach depends on whether the tumour is resectable and the stage and location of the primary tumour. Left-sided CRC arises from the descending colon, and sigmoid colon or distal third of the transverse colon, whereas right-sided CRC arises from the ascending colon or proximal two thirds of the transverse colon. Stages are defined by the TNM staging X, Y and Z. Surgical removal of tumours is followed by consolidation chemotherapy. Non-resectable tumours are treated with induction chemotherapy combined with immunotherapy.