Early Onset Metastatic Colorectal Cancer: Current Insights and Clinical Management of a Rising Condition

Abstract

Despite a recent overall decrease in colorectal cancer (CRC) incidence and mortality, there has been a significant rise in CRC diagnoses in young adults. Early onset colorectal cancer (EOCRC) is defined as CRC diagnosed before the age of 50. Possible predisposing conditions include not only genetic syndromes but also other risk factors, such as microbiome alteration, antibiotic exposure, obesity, diabetes mellitus, and inflammatory bowel disease. EOCRC tends to be diagnosed later than in the older counterpart because of a lack of awareness and the fact that screening for CRC usually starts at the age of 50. Furthermore, CRC in young adults seems to be related to unique molecular features and more aggressive clinical behavior. This paper aims to provide an in-depth review of this poorly understood subject, with a comprehensive review of the state of the art and considerations for future perspectives.

Unraveling the complexities of early-onset colorectal cancer: a perspective on dietary and microbial influences

“…Liang et al further cast a spotlight on the Western-style diet, reporting a culinary preference among the young compared to older individuals residing in Taiwan, who consume a more traditional Taiwanese diet ( 18 ). This dietary preference emerged as a potent force causing genetic or epigenetic alterations leading to microsatellite instability, a precursor to CRC ( 5 , 19 ). Increases in EOCRC were primarily driven by distal colon and rectal tumors between 2004 and 2013 ( 20 ), and this trend was highlighted through the study by Zheng et al, revealing stronger associations between diet quality and early-onset advanced adenomas in the distal colon and rectum compared to the proximal colon ( 20 ).…”

“…Among these factors, enteric pathogens pose the greatest risk of causing microbial imbalance, thus initiating or worsening tumorigenesis through mechanisms such as chronic inflammation, immune suppression, and the production of cancer-promoting metabolites ( 16 ). Dietary choices, particularly those high in meat and animal fat, have been identified as significant contributors to dysbiosis, fueling the production of genotoxic hydrogen sulfide (H 2 S) and the secretion of bile acids, which metabolize into carcinogenic secondary bile acids ( 19 , 22 ). Notably, distinctions between low-risk and high-risk CRC populations have emerged, with the latter exhibiting an overabundance of proinflammatory bacteria, including Porphyromonas, Fusobacterium, Enterococcaceae, and Bacteroides-Prevotella genera, while beneficial and short-chain fatty acid-producing bacteria like Faecalibacterium prausnitziin , known for its anti-inflammatory properties, are diminished ( 22 ).…”

Survival Analysis of Metastatic Early-Onset Colorectal Cancer Compared to Metastatic Average-Onset Colorectal Cancer: A SEER Database Analysis

“…In the last decade, the incidence of early-onset colorectal cancer (EO-CRC) has increased, accounting for 10% of all new CRC diagnoses [ 3 ]. This prompted the US Preventive Task Force (USPTF) to decrease the age of CRC screening from 50 to 45 years in 2021 [ 4 ].…”

“…Non-modifiable risk factors associated with EO-CRC include hereditary risk factors such as Lynch syndrome, adenomatous polyposis syndrome, cystic fibrosis, and family history of CRC [ 6 ]. Furthermore, the presence of metabolic syndrome increases the risk of EO-CRC by up to 31% in the presence of three comorbid metabolic conditions, including obesity, diabetes mellitus, and dyslipidemia [ 4 ]. Regarding survival rates in EO-CRC, patients in the early stages of disease have a favorable prognosis with a five-year survival rate of 90% declining to 71% for stage III and 14% for stage IV [ 7 ].…”

Prognostic signature of colorectal cancer based on uric acid-related genes

“…Colorectal cancer (CRC) is the third most prevalent and deadly cancer worldwide, with approximately 106 180 new diagnosed cases each year [ 1 ]. Despite great improvements in diagnosis, molecular targeted therapy, immunotherapy, and other therapeutic strategies, the prognosis and survival of patients with CRC remain poor, highlighting the importance of distinguishing the risk of CRC and identifying specific therapeutic targets [ [2] , [3] , [4] ].…”