Background: Early-onset colorectal cancer (EOCRC; age <50 years) is rising in Australia despite improving outcomes in older adults. EOCRC shows a strong birth-cohort effect, disproportionate growth in left-sided and rectal tumours, and more frequent stage III–IV presentation. Most cases occur without a family history, indicating that environmental and biological pressures are accelerating carcinogenesis in otherwise average-risk hosts. Objective: To summarise current evidence on EOCRC aetiology, emphasising microbial, dietary and chemical exposures, and to outline clinical, policy and research priorities for Australia. Discussion: Traditional risks such as obesity, metabolic syndrome, sedentary behaviour, alcohol and smoking likely contribute via insulin resistance, chronic inflammation and IGF-1–mediated signalling, but they do not fully explain the recent acceleration or distal predominance. Hereditary syndromes account for a minority of EOCRC, and tumour driver mutation patterns broadly resemble later-onset colorectal cancer, supporting earlier triggering rather than novel genetics. Convergent evidence implicates gut dysbiosis and exposures that disrupt mucosal defences or cause direct DNA damage. Colibactin-producing Escherichia coli can induce a distinctive mutational signature that appears enriched in early and distal tumours. Microplastics and plasticisers may impair barrier function and promote low-grade inflammation, while PFAS and related endocrine-disrupting chemicals are linked to metabolic and immune perturbation and altered bile acid biology. Cumulative antibiotic exposure, particularly early in life, may reduce microbial diversity and favour pathobionts such as Fusobacterium nucleatum.
Gosavi et al. (Fri,) studied this question.