Abstract
Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.
Highlights
The rising prevalence of early-onset colorectal cancer (EOCRC) has fascinated researchers worldwide for more than 10 years (Siegel et al, 2009)
earlyonset colorectal cancer (EOCRC) in inflammatory bowel disease (IBD) vs controls: 3% vs 0.4%, p
This study reported that the dysbiosis patterns of adjacent tissues of late-onset CRC and colorectal adenoma are similar with fluctuations in the relative abundances of genera Pseudomonas, Streptococcus, Porphyromonas, and Fusobacterium, compared to healthy control
Summary
The rising prevalence of early-onset colorectal cancer (EOCRC) has fascinated researchers worldwide for more than 10 years (Siegel et al, 2009). A more recent population-based case–control study of 175 patients with EOCRC and 253 healthy controls failed to show any risk association of EOCRC with obesity (odds ratio [OR]: 0.59 [0.34–1.01]), alcohol consumption (OR: 1.07 [0.49– 2.32]), cigarette smoking (OR: 0.79 [0.40–1.57]), and diabetes mellitus (OR: 1.75 [0.57–5.32]) (Chang et al, 2021). Some dietary habits, such as low intake of fruits, vegetables, and fibers and high intake of red meat and processed meat, are associated with lateonset CRC but are not well established in EOCRC. No definite risk factor can be solely attributed to the pathogenesis of EOCRC; the pathogenesis is more likely due to a complex interaction of the multiple elements involved
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