# Research timeline and gaps: Adiposity and Early-Onset Colorectal Cancer

Selected publication milestones, not an exhaustive history or discovery priority claim.

**2011 — Measured adolescent BMI linked prospectively to later colon risk; exposure age and diagnosis age remain distinct.** [Original PMID22056504](https://pubmed.ncbi.nlm.nih.gov/22056504/).

**2011 — Early-adult BMI associations occur in mismatch-repair carriers and noncarriers; hereditary ascertainment remains separate.** [Original PMID21559014](https://pubmed.ncbi.nlm.nih.gov/21559014/).

**2015 — Early-life fatness associations differ by sex in two cohorts and mainly later-life outcomes.** [Original PMID25777804](https://pubmed.ncbi.nlm.nih.gov/25777804/).

**2016 — Measured adolescent BMI and inflammatory ESR predict later CRC in Swedish men.** [Original PMID25986947](https://pubmed.ncbi.nlm.nih.gov/25986947/).

**2016 — Adult-adiposity MR supports a broader CRC causal link rather than an age-specific intervention effect.** [Original PMID27427428](https://pubmed.ncbi.nlm.nih.gov/27427428/).

**2017 — Unselected EOCRC germline testing finds a real susceptibility subgroup without explaining a secular trend.** [Original PMID27978560](https://pubmed.ncbi.nlm.nih.gov/27978560/).

**2017 — Measured childhood BMI is associated with adult colon, but not rectal, cancer.** [Original PMID28803329](https://pubmed.ncbi.nlm.nih.gov/28803329/).

**2019 — NHSII directly observes a prospective adiposity gradient for CRC before50 in women.** [Original PMID30326010](https://pubmed.ncbi.nlm.nih.gov/30326010/).

**2020 — Isogenic-control human organoid exposure identifies a colibactin mutation signature matching human tumors.** [Original PMID32106218](https://pubmed.ncbi.nlm.nih.gov/32106218/).

**2020 — Sex/site-specific adult-adiposity MR supports overall CRC causality under instrument assumptions.** [Original PMID33327948](https://pubmed.ncbi.nlm.nih.gov/33327948/).

**2021 — Claims-based metabolic syndrome associates with EOCRC but does not isolate adiposity.** [Original PMID33037055](https://pubmed.ncbi.nlm.nih.gov/33037055/).

**2021 — A sulfur-microbial dietary score associates with early adenomas, not a direct clinical cancer outcome.** [Original PMID34273347](https://pubmed.ncbi.nlm.nih.gov/34273347/).

**2022 — Large Swedish antibiotic analysis finds no conclusive overall EOCRC association.** [Original PMID35029165](https://pubmed.ncbi.nlm.nih.gov/35029165/).

**2022 — German early-adult obesity associations use a<55 outcome threshold.** [Original PMID34914944](https://pubmed.ncbi.nlm.nih.gov/34914944/).

**2023 — Age-specific susceptibility GWAS does not constitute MR of adiposity.** [Original PMID36869385](https://pubmed.ncbi.nlm.nih.gov/36869385/).

**2024 — Inherited repair deficiency establishes a distinct high-risk early-cancer context.** [Original PMID38552658](https://pubmed.ncbi.nlm.nih.gov/38552658/).

**2024 — Adhesin perturbation narrows a colibactin carcinogenic mechanism in a predisposed mouse model.** [Original PMID39506107](https://pubmed.ncbi.nlm.nih.gov/39506107/).

**2025 — Human genomic signatures link historical colibactin mutagenesis with younger tumors, distinct from current bacteria.** [Original PMID40267983](https://pubmed.ncbi.nlm.nih.gov/40267983/).

**2025 — Histological reclassification contributes materially to some local young-age incidence trends.** [Original PMID41191353](https://pubmed.ncbi.nlm.nih.gov/41191353/).

**2025 — Early-childhood BMI MR is near-null for all-age CRC, distinguishing timing from adult adiposity.** [Original PMID39587448](https://pubmed.ncbi.nlm.nih.gov/39587448/).

**2026 — Pooled European cohort establishes sex/site heterogeneity but defines early onset as<55.** [Original PMID41422343](https://pubmed.ncbi.nlm.nih.gov/41422343/).

**2026 — AllofUs shows no age-specific BMI interaction; this is not proof of a zero overall effect.** [Original PMID42610385](https://pubmed.ncbi.nlm.nih.gov/42610385/).

**2026 — UPF association concerns early conventional adenomas and not serrated lesions.** [Original PMID41231486](https://pubmed.ncbi.nlm.nih.gov/41231486/).

## Research gaps

A causal-instrument estimate matching strictly under50 CRC and timed prediagnostic adiposity.

Absolute risk and effect heterogeneity by sex, site, ancestry and inherited background without outcome-defined scopes.

Distinguishing childhood adiposity effects from persistent adult exposure and correlated diet/activity.

A valid population decomposition of how much adiposity contributes to secular incidence, separating detection and histological classification.

Independent diet, antibiotic-class/timing and specific microbial exposure causal tests; precursor outcomes and diagnostic signatures remain separate.

Mechanism-specific prevention consequences in humans, without transferring susceptible-mouse or transplanted progression results to spontaneous young-age initiation.

## Boundary experiment

A preregistered consortium analysis combining measured repeated adiposity before diagnosis with an age-stratified valid genetic/natural-experiment design, explicitly reporting colorectal cancer diagnosed before50 and separating adult from childhood exposure, sex, colon/rectum, ancestry, hereditary syndromes and screening/diagnostic contact.