Early-onset colorectal cancer: Current insights and future directions

Abstract

Early-onset colorectal cancer (EOCRC) has seen an alarming rise worldwide over the past two decades. The reason for this global trend is poorly understood. EOCRC appears to have its own unique clinical and molecular features when compared with late-onset colorectal cancer. Younger patients appear to have more distal or rectal disease, a more advanced stage of disease at presentation, and more unfavorable histological features. Identifying risk factors for EOCRC is the first step in mitigating the rising burden of this disease. Here we summarize several noteworthy biological factors and environmental exposures that are postulated to be responsible culprits. This can hopefully translate in clinical practice to the development of better risk stratification tool for identifying high-risk individuals for early colorectal cancer screening, and identifying areas needed for further research to curb this rising trend.

Insights into Early Onset Colorectal Cancer through Analysis of Normal Colon Organoids of Familial Adenomatous Polyposis Patients

“…A number of studies have implicated generational shifts in lifestyle factors as important contributors to the rise of EOCRC within Western populations [ 10 ]. We have previously shown that exposure of normal colon organoids to several different CRC related lifestyle factors led to widespread gene expression differences that are enriched for genes associated with CRC [ 18 , 19 , 20 , 21 , 22 ].…”

“…Given the strong enrichment of the FAP DEGs observed here and CRC, we were not surprised to see that FAP DEGs were also enriched for targets of various CRC lifestyle factors. Importantly, one theory attempting to explain the rise in EOCRC rates observed across recent generations centers on changes in Western lifestyle, including increased alcohol consumption [ 10 ]. As such, we performed qPCR analysis on a subset of genes previously found to be altered following ethanol treatment that were also differentially expressed in FAP colon organoids and in at least one EOCRC dataset.…”

“…The vast majority of EOCRCs are believed to be driven by non-hereditary forms of CRC [ 9 ]. While the causes of these ‘sporadic’ EOCRC remain poorly understood, generational shifts in environment, lifestyle, and dietary habits have been strongly implicated [ 10 ]. For example, a recent study has provided evidence that moderate to high consumption of alcohol is associated with a greater risk of EOCRC than late onset CRC [ 11 ].…”

The hsa_circ_0039857/miR-338-3p/RAB32 axis promotes the malignant progression of colorectal cancer

“…CRC occurrence and development are caused by complex biological processes, including gene mutation, imbalance of cell proliferation, differentiation and apoptosis. [ 27 ]. Therefore, further searching for high-sensitivity, high-specificity, and high-stability diagnostic markers and possible targets for clinical treatment is particularly important for the development of CRC.…”

The Molecular Genetics of Colorectal Cancer, Hereditary Colorectal Cancer Syndromes, and Early-Onset Colorectal Cancer

“…Mutations in APC, MMR genes, and MUTYH are known drivers of hereditary CRC syndromes and are represented in EOCRC patients. 75 However, there are also non–colorectal-related germline mutations that predispose to EOCRC, including variants in BRCA1, BRCA2, TP53, and EGFR. 64 Up to 29% of EOCRC tumors are MSI-H, compared with 15% of all CRC, and this accounts for patients with and without Lynch syndrome.…”