Molecular Aspects of Colorectal Adenomas: The Interplay among Microenvironment, Oxidative Stress, and Predisposition

Table 1

Possible risk factors associated with colorectal adenoma onset.

Risk factors	Effects on adenoma onset	References
Age	Possible onset before 50 years	[26, 27]
	Major incidence after 50 years	[28]
	Peak at 70 years	[16]
Gender	Higher incidence in males than in females	[16, 29]
Ethnicity	High incidence in Western and African Americans populations	[4, 30, 31]
Persistent organic pollutants
Organochlorine pesticides	Wnt and Hedgehog/Gli1 pathway activation. Increased ROS	[32]
Dichlorodiphenyldichloroethylene
Polychlorinated biphenyls	Predisposition to gut inflammation	[33]
Dioxin-like PBS126
Heavy metals
Arsenic	Altered gut-associated immunity and microbiome	[34]
Cadmium	Intestinal inflammation, modified microbiome	[35]
Antibiotics	Changes in gut microbiota	[36]
Food additives	Changes in gut microbiota	[36]
Diet
Excessive processed red meat consumption	Gut dysbiosis by HCA and PAH production. Heme iron associated with aldehyde generation	[37–40]
High saturated fat intake	Intestinal inflammation	[41–43]
Lifestyles
Stress	Increased stress hormones, altered rate of cell growth	[44, 45]
Lack of physical exercise	Overweight and obesity	[46]
Obesity	High TNF-α, IGF-1, and adiponectin	[47]
Cigarette smoking	Oxidative stress, chronic inflammation, genetic/epigenetic alterations by BaP/HCA generation	[25, 48–50]
Heavy alcohol drinking	Production of acetaldehyde	[51]
Gut microbiota alterations
Fusobacterium nucleatum	Colon cells adhesion by FadA, β-catenin activation	[52]
Escherichia coli	Inflammation and DNA breaks by CDT and colibactin	[51]
Bacteroides fragilis	Wnt pathway activation by BFT. ROS production	[53]
Enterococcus faecalis	Superoxide production	[54]
Helicobacter pylori	Increased serrated polyps	[55]

Bacteroides fragilis toxin (BFT); cytolethal distending toxin (CDT); heterocyclic amines (HCAs); polycyclic aromatic hydrocarbons (PAHs); benzo[a]pyrene (BaP).