Traditional Risk Factors Are Not Associated with the Rise of Early-Onset Colorectal Cancer: An All of Us Study: GI Signals

Colorectal retrospective · n=12,275 · Aug 18, 2026 · Dis Colon Rectum · IF 3.5

Traditional Risk Factors Are Not Associated with the Rise of Early-Onset Colorectal Cancer: An All of Us Study.

Epidemiologycolorectal cancerepidemiology

Clinical takeawayThis negative finding reveals that traditional environmental and genetic risk factors do not explain the rising incidence of early-onset colorectal cancer. Do not use their absence to reassure younger patients about CRC risk. Family history remains significantly associated (OR 2.10) and should guide risk assessment. Current risk models are incomplete; novel environmental or early-life exposures likely drive early-onset disease but remain unidentified.

What it foundFamily history was associated with higher colorectal cancer odds uniformly across ages (OR 2.10, 95% CI 1.69-2.61), but heavy smoking during ages 20-40, alcohol use disorders, BMI, and 283 established genetic variants demonstrated no age-specific associations with early-onset disease.

ContextChallenges the assumption that traditional environmental risk factors (smoking, alcohol, obesity) explain the rising early-onset CRC incidence. Current risk stratification models may fail to identify younger patients at true risk, indicating that preventable or modifiable exposures causing the rise remain unknown.

Refinessuggested applicable standard· American Gastroenterological Association, 'AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis', 2020

Decision at stakeCounsel against smoking to prevent colorectal cancer risk

… In Crohn's disease, prioritize cessation as a disease-modifying intervention equal to biologics; in ulcerative colitis, counsel against smoking despite the paradoxical protective effect because cancer and cardiovascular risks outweigh it. …

From our summary of this standard, unedited — the part the paper bears on. … marks omitted text. Our wording, not the guideline's; read the source for its own text.

Our full summary of this standard

Address tobacco use at every visit using the 5 A's framework (Ask, Advise, Assess, Assist, Arrange) and combine behavioral support with pharmacotherapy; varenicline is the most effective single agent, and combination NRT (patch plus gum/lozenge) is effective. Set a quit date within 2 weeks, start pharmacotherapy 1-2 weeks before the quit date, and schedule follow-up at 1 week, 1 month, and 3 months. In Crohn's disease, prioritize cessation as a disease-modifying intervention equal to biologics; in ulcerative colitis, counsel against smoking despite the paradoxical protective effect because cancer and cardiovascular risks outweigh it. For patients with inadequate response to monotherapy, consider combining varenicline with NRT based on individual assessment, though evidence for superiority over single agents is inconsistent.

American Gastroenterological Association, 'AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis', 2020 · reviewed 2026-07-21 ↗

Nigam A … Goffredo P · Diseases of the Colon and Rectum · IF 3.5 · PubMed ↗Permalink