Early-onset colorectal cancer rates are projected to reach 11% of all colon and 23% of rectal cancer cases by 2030, according to a recent study. 

In the United States, the incidence of early-onset colorectal cancer (EO-CRC) among individuals under 50 years has increased, contrasting with decreasing rates in older populations caused by systematic screening after age 50.

In the new review, published in Cellular and Molecular Gastroenterology and Hepatology, investigators examined the genetic, lifestyle, and environmental risk factors contributing to EO-CRC and highlighted molecular pathways specific to this subtype.

Approximately 20% of EO-CRC cases were found to be associated with hereditary mutations, indicating that the majority of cases may be sporadic in nature and may involve varied molecular characteristics. EO-CRC frequently involved mutations in genes like CTNNB1, associated with the Wnt/β-catenin pathway, and abnormalities in the PI3K/AKT signaling pathway, both of which promote tumorigenesis through cell proliferation and metabolic dysregulation.

Obesity was also indicated to be a prominent risk factor, nearly doubling EO-CRC risk, while type 2 diabetes was associated with a 24% increased risk. A Western diet high in fat and sugar, along with alcohol and tobacco use, further elevated EO-CRC risk. Additionally, gut dysbiosis, characterized by an overrepresentation of Fusobacterium and Peptostreptococcus species, has been identified in EO-CRC cases, suggesting an association between microbiome alterations and disease etiology.

Clinically, patients with EO-CRC often present with advanced-stage, poorly differentiated rectal or left-sided tumors, which are typically difficult to treat. Prognosis is better for early-stage (stages I and II) EO-CRC compared with late-stage cases. Noninvasive biomarker assays and microbiome-based screenings are being evaluated to improve early diagnosis in younger populations.

The association of EO-CRC with advanced-stage, poorly differentiated tumors and distinct pathophysiology suggested potential benefits from age-adjusted screening guidelines and further research into gene-environment interactions.

Full disclosures can be found in the published study. This journal pre-proof version includes formatting enhancements for readability but is not the final published version, as it will undergo further editing, typesetting, and review, during which errors may still be identified; all journal disclaimers apply.