Table 1:
Risk factors of early-onset colorectal cancer
| Risk factor (direction of risk) | Hypothesized mechanism | Supporting evidence |
|---|---|---|
|
| ||
| Metabolic syndrome (+) | Increased risk in cohort, case-control studies, and meta-analyses | |
| Obesity (+) | Chronic inflammation mediated by adipocytokines (TNF-α, IL-6, CRP) trigger immune response; abnormal signaling pathways in insulin-like growth factors and sex hormones | Trend towards increased risk among cohort, case-control, and meta-analyses studies |
| Type 2 diabetes (+/−) | Impaired insulin receptor activation, high levels of insulin-like growth factors stimulate colonic mucosal cell growth and prevent apoptosis | Inconsistent results in few case-control studies |
| Dyslipidemia (?) | Triglycerides may increase fecal bile acid exposure or energy for neoplastic cells; cholesterol accumulates in membranes of cancer cells | Insufficient evidence |
| Hypertension (?) | Unclear, possibly prevents apoptosis | Insufficient evidence |
| Dietary patterns (+) | Increased risk in cohort, case-control studies, and meta-analyses | |
| Low fiber diet (+) | Decreased colonic motility causing increased exposure to fecal carcinogens; stimulates butyrogenic activity, which is anti-neoplastic | Increased risk in cohort, case-control studies, and meta-analyses |
| Sugar-sweetened beverages (+) | Induce insulin resistance; fructose may cause dysbiosis and increase gut permeability | Increased risk in few cohort studies |
| Red/processed meats (+) | Exposure to mutagenic compounds including N-nitroso compounds, heterocyclic amines, polycyclic aromatic hydrocarbons | Increased risk in cohort, case-control studies, and meta-analyses |
| High fat diet (+) | Increased bile acid metabolism with bile acid conversion to deoxycholic acid | Increased risk in cohort, case-control studies, and meta-analyses |
| Micronutrients | ||
| Calcium (?) | Prevents fatty acid/bile acid carcinogenic on intestinal mucosa; inhibits inflammation | Insufficient evidence |
| Vitamin D (−) | Inhibits proliferation and angiogenesis, promotes differentiation; vit D receptor binding inhibits Wnt/β-catenin pathway | Limited; decreased risk in cohort study |
| Alcohol use (+) | Direct and indirect genotoxic effects by metabolites | Increased risk in cohort, case-control studies, and meta-analyses |
| Smoking and tobacco (+/−) | Exposure to genotoxic compounds through circulatory system or direct ingestion leads to colorectal adenoma | Inconsistent results in cohort, case-control studies, and meta-analyses |
| Sedentary behavior (+/−) | Decreased colonic motility causing increased exposure to fecal carcinogens; impairment of glucose homeostasis; increased levels of pro-inflammatory factors, decreased levels of anti-inflammatory factors | Inconsistent results in few studies |
| Maternal weight gain/obesity (+) | Fetal programming leading to changes in adipose tissue and insulin sensitivity; epigenetic methylation of genes involved in energy metabolism | Limited; increased risk in cohort study |
| Birth weight (+) | Increased risk of obesity in adulthood | Limited; increased risk in cohort study |
| Dietary additives (?) | Variable | Insufficient evidence |
| Intestinal dysbiosis | Biofilm formation, increased inflammation, gut permeability | |
| Bacteria (+) | Potential oncogenic associations with Fusobacterium, B. fragilis, S. gallolytics, H. pylori | Meta-analysis with increased Fusobacterium in eoCRC patients |
| Antibiotic use (?) | Modifies intestinal flora | Insufficient evidence |