Etiology and Epidemiological Trends of Early-Onset Colorectal Cancer

Abstract

Early-onset colorectal cancer (EOCRC), diagnosed before age 50 years, is increasing in many countries. This narrative review examines whether dietary carcinogen exposure or chronic inflammation is better supported as a contributor, and whether the two can be separated at all. Mechanistic studies describe three diet-linked routes to colonic DNA damage: heat-generated mutagens (heterocyclic amines and polycyclic aromatic hydrocarbons), heme-associated nitrosation and lipid peroxidation, and colibactin produced by pks-positive Escherichia coli. This work establishes biological plausibility and genotoxicity, but it does not show that these exposures caused the population-level rise. Ecological data show EOCRC increasing in regions with Westernized diets, whereas diagnosed pediatric inflammatory bowel disease (IBD) corresponds only loosely with EOCRC patterns. That comparison is limited by temporal misalignment, registry differences, and the fact that an IBD diagnosis does not capture subclinical or metabolic inflammation. Rising early-onset gastric cancer and falling colitis-associated colorectal cancer fit a dietary-exposure hypothesis but do not test it. Colibactin-producing bacteria and inflammation may reinforce each other, so the two factors are unlikely to act independently. Current evidence therefore supports dietary carcinogen exposure as a plausible leading contributor and inflammation as a possible amplifier, but this ordering remains a hypothesis. Priorities include defining exposure windows, quantifying dose-response relationships, and improving registry data.